Accession ID: MIRT001190 [miRNA, hsa-miR-21-5p :: PTEN, target gene]
pre-miRNA Information
pre-miRNA ID hsa-mir-21LinkOut: [miRBase ]
Synonyms MIRN21, hsa-mir-21, miR-21, miRNA21, MIR21
Description Homo sapiens miR-21 stem-loop
Comment Mourelatos et al. named this sequence miR-21 precursor-17 and also reported the exact reverse complement of this predicted stem-loop sequence and erroneously assigned the name miR-104 .
2nd Structure of pre-miRNA
Disease
Mature miRNA Information
Mature miRNA hsa-miR-21-5p
Mature Sequence 8| UAGCUUAUCAGACUGAUGUUGA |29
Evidence Experimental
Experiments Northern
Putative hsa-miR-21-5p Targets LinkOut: [ TargetScanS 5.1 | MicroCosm | microRNA.org | miRecords | miRDB | miRo | miRNAMap 2.0 ]
Gene Information
Gene Symbol PTEN LinkOut: [ Entrez Gene | BioGPS | Wikipedia | iHop ]
Synonyms 10q23del, BZS, DEC, MGC11227, MHAM, MMAC1, PTEN1, TEP1
Description phosphatase and tensin homolog
Transcript NM_0003    LinkOut: [ RefSeq ]
Expression LinkOut: [ BioGPS ]
Putative miRNA Targets on PTEN LinkOut: [ TargetScan 5.1 | MicroCosm | miRNAMap 2.0 ]
3'UTR of PTEN
(miRNA target sites are highlighted)
>PTEN|NM_0003|3'UTR
   1 TGAATTTTTTTTTATCAAGAGGGATAAAACACCATGAAAATAAACTTGAATAAACTGAAAATGGACCTTTTTTTTTTTAA
  81 TGGCAATAGGACATTGTGTCAGATTACCAGTTATAGGAACAATTCTCTTTTCCTGACCAATCTTGTTTTACCCTATACAT
 161 CCACAGGGTTTTGACACTTGTTGTCCAGTTGAAAAAAGGTTGTGTAGCTGTGTCATGTATATACCTTTTTGTGTCAAAAG
 241 GACATTTAAAATTCAATTAGGATTAATAAAGATGGCACTTTCCCGTTTTATTCCAGTTTTATAAAAAGTGGAGACAGACT
 321 GATGTGTATACGTAGGAATTTTTTCCTTTTGTGTTCTGTCACCAACTGAAGTGGCTAAAGAGCTTTGTGATATACTGGTT
 401 CACATCCTACCCCTTTGCACTTGTGGCAACAGATAAGTTTGCAGTTGGCTAAGAGAGGTTTCCGAAGGGTTTTGCTACAT
 481 TCTAATGCATGTATTCGGGTTAGGGGAATGGAGGGAATGCTCAGAAAGGAAATAATTTTATGCTGGACTCTGGACCATAT
 561 ACCATCTCCAGCTATTTACACACACCTTTCTTTAGCATGCTACAGTTATTAATCTGGACATTCGAGGAATTGGCCGCTGT
 641 CACTGCTTGTTGTTTGCGCATTTTTTTTTAAAGCATATTGGTGCTAGAAAAGGCAGCTAAAGGAAGTGAATCTGTATTGG
 721 GGTACAGGAATGAACCTTCTGCAACATCTTAAGATCCACAAATGAAGGGATATAAAAATAATGTCATAGGTAAGAAACAC
 801 AGCAACAATGACTTAACCATATAAATGTGGAGGCTATCAACAAAGAATGGGCTTGAAACATTATAAAAATTGACAATGAT
 881 TTATTAAATATGTTTTCTCAATTGTAACGACTTCTCCATCTCCTGTGTAATCAAGGCCAGTGCTAAAATTCAGATGCTGT
 961 TAGTACCTACATCAGTCAACAACTTACACTTATTTTACTAGTTTTCAATCATAATACCTGCTGTGGATGCTTCATGTGCT
1041 GCCTGCAAGCTTCTTTTTTCTCATTAAATATAAAATATTTTGTAATGCTGCACAGAAATTTTCAATTTGAGATTCTACAG
1121 TAAGCGTTTTTTTTCTTTGAAGATTTATGATGCACTTATTCAATAGCTGTCAGCCGTTCCACCCTTTTGACCTTACACAT
1201 TCTATTACAATGAATTTTGCAGTTTTGCACATTTTTTAAATGTCATTAACTGTTAGGGAATTTTACTTGAATACTGAATA
1281 CATATAATGTTTATATTAAAAAGGACATTTGTGTTAAAAAGGAAATTAGAGTTGCAGTAAACTTTCAATGCTGCACACAA
1361 AAAAAAGACATTTGATTTTTCAGTAGAAATTGTCCTACATGTGCTTTATTGATTTGCTATTGAAAGAATAGGGTTTTTTT
1441 TTTTTTTTTTTTTTTTTTTTTTAAATGTGCAGTGTTGAATCATTTCTTCATAGTGCTCCCCCGAGTTGGGACTAGGGCTT
1521 CAATTTCACTTCTTAAAAAAAATCATCATATATTTGATATGCCCAGACTGCATACGATTTTAAGCGGAGTACAACTACTA
1601 TTGTAAAGCTAATGTGAAGATATTATTAAAAAGGTTTTTTTTTCCAGAAATTTGGTGTCTTCAAATTATACCTTCACCTT
1681 GACATTTGAATATCCAGCCATTTTGTTTCTTAATGGTATAAAATTCCATTTTCAATAACTTATTGGTGCTGAAATTGTTC
1761 ACTAGCTGTGGTCTGACCTAGTTAATTTACAAATACAGATTGAATAGGACCTACTAGAGCAGCATTTATAGAGTTTGATG
1841 GCAAATAGATTAGGCAGAACTTCATCTAAAATATTCTTAGTAAATAATGTTGACACGTTTTCCATACCTTGTCAGTTTCA
1921 TTCAACAATTTTTAAATTTTTAACAAAGCTCTTAGGATTTACACATTTATATTTAAACATTGATATATAGAGTATTGATT
2001 GATTGCTCATAAGTTAAATTGGTAAAGTTAGAGACAACTATTCTAACACCTCACCATTGAAATTTATATGCCACCTTGTC
2081 TTTCATAAAAGCTGAAAATTGTTACCTAAAATGAAAATCAACTTCATGTTTTGAAGATAGTTATAAATATTGTTCTTTGT
2161 TACAATTTCGGGCACCGCATATTAAAACGTAACTTTATTGTTCCAATATGTAACATGGAGGGCCAGGTCATAAATAATGA
2241 CATTATAATGGGCTTTTGCACTGTTATTATTTTTCCTTTGGAATGTGAAGGTCTGAATGAGGGTTTTGATTTTGAATGTT
2321 TCAATGTTTTTGAGAAGCCTTGCTTACATTTTATGGTGTAGTCATTGGAAATGGAAAAATGGCATTATATATATTATATA
2401 TATAAATATATATTATACATACTCTCCTTACTTTATTTCAGTTACCATCCCCATAGAATTTGACAAGAATTGCTATGACT
2481 GAAAGGTTTTCGAGTCCTAATTAAAACTTTATTTATGGCAGTATTCATAATTAGCCTGAAATGCATTCTGTAGGTAATCT
2561 CTGAGTTTCTGGAATATTTTCTTAGACTTTTTGGATGTGCAGCAGCTTACATGTCTGAAGTTACTTGAAGGCATCACTTT
2641 TAAGAAAGCTTACAGTTGGGCCCTGTACCATCCCAAGTCCTTTGTAGCTCCTCTTGAACATGTTTGCCATACTTTTAAAA
2721 GGGTAGTTGAATAAATAGCATCACCATTCTTTGCTGTGGCACAGGTTATAAACTTAAGTGGAGTTTACCGGCAGCATCAA
2801 ATGTTTCAGCTTTAAAAAATAAAAGTAGGGTACAAGTTTAATGTTTAGTTCTAGAAATTTTGTGCAATATGTTCATAACG
2881 ATGGCTGTGGTTGCCACAAAGTGCCTCGTTTACCTTTAAATACTGTTAATGTGTCATGCATGCAGATGGAAGGGGTGGAA
2961 CTGTGCACTAAAGTGGGGGCTTTAACTGTAGTATTTGGCAGAGTTGCCTTCTACCTGCCAGTTCAAAAGTTCAACCTGTT
3041 TTCATATAGAATATATATACTAAAAAATTTCAGTCTGTTAAACAGCCTTACTCTGATTCAGCCTCTTCAGATACTCTTGT
3121 GCTGTGCAGCAGTGGCTCTGTGTGTAAATGCTATGCACTGAGGATACACAAAAATACCAATATGATGTGTACAGGATAAT
3201 GCCTCATCCCAATCAGATGTCCATTTGTTATTGTGTTTGTTAACAACCCTTTATCTCTTAGTGTTATAAACTCCACTTAA
3281 AACTGATTAAAGTCTCATTCTTGTCAAAAAAAAAAAAAAAAAAAAAAAAAAA
Target sites Provided by authors  Predicted by miRanda
miRNA-target interactions (Predicted by miRanda)
IDDuplex structurePositionScoreMFE
1
miRNA  3' aguugUAGUCA--GACUAUUCGAu 5'
               ||:: |  || |||||:| 
Target 5' tattgATTGATTGCTCATAAGTTa 3'
1993 - 2016 135.00 -6.90
2
miRNA  3' agUUGUAGUCAGACUAUUCGAu 5'
            ::|| ||    ||||||:| 
Target 5' gtGGCAACA----GATAAGTTt 3'
423 - 440 134.00 -9.41
3
miRNA  3' agUUGUAGUCAGACUAUUCGAu 5'
            ||:: || | | ||::||| 
Target 5' atAATGACATTATAATGGGCTt 3'
2234 - 2255 128.00 -7.60
Experimental Support 1 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method Northern blot , qRT-PCR , Western blot , Other , Reporter assay
Conditions KMCH-1 , mz-ChA-1 , TFK
Disease Cholangiocarcinoma;
Location of target site 3'UTR
Tools used in this research mirVana
Original Description (Extracted from the article) ... Our studies identify several miRNA that are consistently altered in expression in malignant cholangio-cytes. ...

- Meng, F. Henson, R. Lang, M. Wehbe, H. et al., 2006, Gastroenterology.

Article - Meng, F. Henson, R. Lang, M. Wehbe, H. et al.
- Gastroenterology, 2006
BACKGROUND & AIMS: Micro-RNA (miRNA) are endogenous regulatory RNA molecules that modulate gene expression. Alterations in miRNA expression can contribute to tumor growth by modulating the functional expression of critical genes involved in tumor cell proliferation or survival. Our aims were to identify specific miRNA involved in the regulation of cholangiocarcinoma growth and response to chemotherapy. METHODS: miRNA expression in malignant and nonmalignant human cholangiocytes was assessed using a microarray. Expression of selected miRNA and their precursors was evaluated by Northern blots and real-time polymerase chain reaction, respectively. The effect of selected miRNA on cell growth and response to chemotherapy was assessed using miRNA-specific antisense oligonucleotides to decrease miRNA expression or with precursor miRNA to increase cellular expression. RESULTS: miRNA expression was markedly different in malignant cholangiocytes, with decreased expression of many miRNA compared with nonmalignant cells. A cluster of miRNA, including miR-320, miR-200b, miR-21, miR-23a, miR-141, miR-27a, and miR-34a, were expressed in all cell lines. MiR-21, miR-141, and miR-200b were highly over-expressed in malignant cholangiocytes. Inhibition of miR-21 and miR-200b increased sensitivity to gemcitabine, whereas inhibition of miR-141 decreased cell growth. Treatment of tumor cell xenografts with systemic gemcitabine altered the expression of a significant number of miRNA. miR-21 modulates gemcitabine-induced apoptosis by phosphatase and tensin homolog deleted on chromosome 10 (PTEN)-dependent activation of PI 3-kinase signaling. Potential target genes that were modulated by selected miRNA were identified. CONCLUSIONS: Alterations in miRNA expression contribute to tumor growth and response to chemotherapy. Aberrantly expressed miRNA or their targets will provide mechanistic insight and therapeutic targets for cholangiocarcinoma.
LinkOut: [PMID: 16762633]
Experimental Support 2 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method Other
Article - Ji, R. Cheng, Y. Yue, J. Yang, J. Liu, X. et al.
- Circ Res, 2007
MicroRNAs (miRNAs) are a recently discovered class of endogenous, small, noncoding RNAs that regulate about 30% of the encoding genes of the human genome. However, the role of miRNAs in vascular disease is currently completely unknown. Using microarray analysis, we demonstrated for the first time that miRNAs are aberrantly expressed in the vascular walls after balloon injury. The aberrantly expressed miRNAs were further confirmed by Northern blot and quantitative real-time polymerase chain reaction. Modulating an aberrantly overexpressed miRNA, miR-21, via antisense-mediated depletion (knock-down) had a significant negative effect on neointimal lesion formation. In vitro, the expression level of miR-21 in dedifferentiated vascular smooth muscle cells was significantly higher than that in fresh isolated differentiated cells. Depletion of miR-21 resulted in decreased cell proliferation and increased cell apoptosis in a dose-dependent manner. MiR-21-mediated cellular effects were further confirmed in vivo in balloon-injured rat carotid arteries. Western blot analysis demonstrated that PTEN and Bcl-2 were involved in miR-21-mediated cellular effects. The results suggest that miRNAs are novel regulatory RNAs for neointimal lesion formation. MiRNAs may be a new therapeutic target for proliferative vascular diseases such as atherosclerosis, postangioplasty restenosis, transplantation arteriopathy, and stroke.
LinkOut: [PMID: 17478730]
Experimental Support 3 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method Immunocytochemistry , Luciferase reporter assay , Northern blot , qRT-PCR , Western blot , Microarray , Other , Reporter assay
Conditions HCC , SK-HEP-1 , SNU-182
Disease Hepatocellular cancer;
Location of target site 3'UTR
Tools used in this research Target prediction algorithm
Original Description (Extracted from the article) ... PTEN is a target for miR-21//3'-UTR of PTEN contains a target that is modulated by miR-21 ...

- Meng, F. Henson, R. Wehbe-Janek, H. et al., 2007, Gastroenterology.

Article - Meng, F. Henson, R. Wehbe-Janek, H. et al.
- Gastroenterology, 2007
BACKGROUND AND AIMS: microRNAs (miRNAs) are short noncoding RNAs that regulate gene expression negatively. Although a role for aberrant miRNA expression in cancer has been postulated, the pathophysiologic role and relevance of aberrantly expressed miRNA to tumor biology has not been established. METHODS: We evaluated the expression of miRNA in human hepatocellular cancer (HCC) by expression profiling, and defined a target gene and biologically functional effect of an up-regulated miRNA. RESULTS: miR-21 was noted to be highly overexpressed in HCC tumors and cell lines in expression profiling studies using a miRNA microarray. Inhibition of miR-21 in cultured HCC cells increased expression of the phosphatase and tensin homolog (PTEN) tumor suppressor, and decreased tumor cell proliferation, migration, and invasion. In contrast-enhanced miR-21 expression by transfection with precursor miR-21 increased tumor cell proliferation, migration, and invasion. Moreover, an increase in cell migration was observed in normal human hepatocytes transfected with precursor miR-21. PTEN was shown to be a direct target of miR-21, and to contribute to miR-21 effects on cell invasion. Modulation of miR-21 altered focal adhesion kinase phosphorylation and expression of matrix metalloproteases 2 and 9, both downstream mediators of PTEN involved in cell migration and invasion. CONCLUSIONS: Aberrant expression of miR-21 can contribute to HCC growth and spread by modulating PTEN expression and PTEN-dependent pathways involved in mediating phenotypic characteristics of cancer cells such as cell growth, migration, and invasion.
LinkOut: [PMID: 17681183]
Experimental Support 4 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method Other
Article - Pezzolesi, M. G. Platzer, P. Waite, K. A. Eng, C.
- Am J Hum Genet, 2008
Germline mutations in the gene encoding phosphatase and tensin homolog deleted on chromosome ten (PTEN [MIM 601728]) are associated with a number of clinically distinct heritable cancer syndromes, including both Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRRS). Seemingly identical pathogenic PTEN mutations have been observed in patients with CS and BRRS, as well as in patients with incomplete features of CS, referred to as CS-like (CSL) patients. These observations indicate that additional, unidentified, genetic and epigenetic factors act as phenotypic modifiers in these disorders. These genetic factors could also contribute to disease in patients with CS, CSL, or BRRS without identifiable PTEN mutations. Two potential modifiers are miR-19a and miR-21, which are previously identified PTEN-targeting miRNAs. We investigated the role of these miRNAs by characterizing their relative expression levels in PTEN-mutation-positive and PTEN-mutation-negative patients with CS, CSL, or BRRS. Interestingly, we observed differential expression of miR-19a and miR-21 in our PTEN-mutation-positive patients. Both were found to be significantly overexpressed within this group (p < 0.01) and were inversely correlated with germline PTEN protein levels. Similarly, the relative expression of miR-19a and miR-21 was differentially expressed in a series of PTEN-mutation-negative patients with CS or CSL with variable clinical phenotypes and decreased full-length PTEN protein expression. Among PTEN-mutation-positive patients with CS, both miRNAs were significantly overexpressed (p = 0.006-0.013). Taken together, our study results suggest that differential expression of PTEN-targeting miR-19a and miR-21 modulates the PTEN protein levels and the CS and CSL phenotypes, irrespective of the patient's mutation status, and support their roles as genetic modifiers in CS and CSL.
LinkOut: [PMID: 18460397]
Experimental Support 5 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method Luciferase reporter assay , qRT-PCR , Western blot ,
Location of target site 3'UTR
Original Description (Extracted from the article) ... The miR-21-mediated downregulation of PDCD4 is required for full induction of AP-1 activity in response to RAS//Having shown that PDCD4 is downregulated by the RAS-induced miR-21 (Figure 6c) and that PDCD4 inhibits AP-1 (Figures 7a and b)//In our RAS-inducible cell system, transcriptional inhibition does not seem to play a major role in the downregulation of PTEN, as the effect of RAS is entirely relieved by the inhibition of miR-21 (Figure 7c) ...

- Talotta, F. Cimmino, A. Matarazzo, M. R. et al., 2009, Oncogene.

Article - Talotta, F. Cimmino, A. Matarazzo, M. R. et al.
- Oncogene, 2009
The transcription factor AP-1 plays key roles in tumorigenesis, by regulating a variety of protein-coding genes, implicated in multiple hallmarks of cancer. Among non-coding genes, no AP-1 target has been described yet in tumorigenesis. MicroRNAs (miRNAs) are negative post-transcriptional regulators of protein-coding genes. miRNA expression signatures are highly relevant in cancer and several tumor-associated miRNAs (oncomirs) play critical roles in oncogenesis. Here, we show that the miRNA miR-21, which represents the most frequently upregulated oncomir in solid tumors, is induced by AP-1 in response to RAS. By analyzing validated miR-21 targets, we have found that the tumor suppressors PTEN and PDCD4 are downregulated by RAS in an AP-1- and miR-21-dependent fashion. We further show that, given the role of PDCD4 as negative regulator of AP-1, the miR-21-mediated downregulation of PDCD4 is essential for the maximal induction of AP-1 activity in response to RAS. Our data reveal a novel mechanism of positive autoregulation of the AP-1 complex in RAS transformation and disclose the function of oncomirs as critical targets and regulators of AP-1 in tumorigenesis.
LinkOut: [PMID: 18850008]
Experimental Support 6 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method Luciferase reporter assay , Other
Conditions Hep G2 , HPH
Location of target site 3'UTR
Original Description (Extracted from the article) ... PTEN mRNA has been identified through bioinformatics and experimental approaches as a target for microRNA-21 (miR-21), whose “seed” sequence (base 2-9 of the 5 end) shares 85% homology with PTEN mRNA (seven of eight bases; nucleotides 2672-2678)(Fig. 4A).//These results indicate that OA triggers PTEN mRNA degradation in hepatocytes by up-regulating miR-21, which specifically targets PTEN mRNA, through mTOR/NF-B–dependent mechanisms. ...

- Vinciguerra, M. Sgroi, A. Veyrat-Durebex, et al., 2009, Hepatology.

Article - Vinciguerra, M. Sgroi, A. Veyrat-Durebex, et al.
- Hepatology, 2009
Phosphatase and tensin homolog (PTEN) is a regulator of phosphoinositide 3-kinase signaling and an important tumor suppressor mutated/deleted in human cancers. PTEN deletion in the liver leads to insulin resistance, steatosis, inflammation, and cancer. We recently demonstrated that unsaturated fatty acids trigger steatosis by down-regulating PTEN expression in hepatocytes via activation of a mammalian target of rapamycin (mTOR)/nuclear factor kappa B (NF-kappaB) complex, but the molecular mechanisms implicated in this process are still unknown. Here, we investigated potential genetic and epigenetic mechanisms activated by fatty acids leading to PTEN down-regulation. Our results indicate that unsaturated fatty acids down-regulate PTEN messenger RNA expression in hepatocytes through mechanisms unrelated to methylation of the PTEN promoter, histone deacetylase activities, or repression of the PTEN promoter activity. In contrast, unsaturated fatty acids up-regulate the expression of microRNA-21, which binds to PTEN messenger RNA 3'-untranslated region and induces its degradation. The promoter activity of microRNA-21 was increased by mTOR/NF-kappaB activation. Consistent with these data, microRNA-21 expression was increased in the livers of rats fed high-fat diets and in human liver biopsies of obese patients having diminished PTEN expression and steatosis. CONCLUSION: Unsaturated fatty acids inhibit PTEN expression in hepatocytes by up-regulating microRNA-21 synthesis via an mTOR/NF-kappaB-dependent mechanism. Aberrant up-regulation of microRNA-21 expression by excessive circulating levels of fatty acids exemplify a novel regulatory mechanism by which fatty acids affect PTEN expression and trigger liver disorders.
LinkOut: [PMID: 19072831]
Experimental Support 7 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method Microarray , immunohistochemistry
Conditions Gastric tumor/non-tumor
Tools used in this research miRanda , PicTar , TargetScan
Article - Guo, J. Miao, Y. Xiao, B. Huan, R. Jiang, et al.
- J Gastroenterol Hepatol, 2009
BACKGROUND AND AIM: MicroRNAs (miRNAs) play important roles in carcinogenesis. The global miRNA expression profile of gastric cancer has not been reported. The purpose of the present study was to determine the miRNA expression profile of gastric cancer. METHODS: Total RNA were first extracted from primary gastric cancer tissues and adjacent non-tumorous tissues and then small isolated RNAs (< 300 nt) were 3'-extended with a poly(A) tail. Hybridization was carried out on a microParaflo microfluidic chip (LC Sciences, Houston, TX, USA). After hybridization detection by fluorescence labeling using tag-specific Cy3 and Cy5 dyes, hybridization images were collected using a laser scanner and digitized using Array-Pro image analysis software (Media Cybernetics, Silver Spring, MD, USA). To validate the results and investigate the biological meaning of differential expressed miRNAs, immunohistochemistry was used to detect the differential expression of target genes. RESULTS: The most highly expressed miRNAs in non-tumorous tissues were miR-768-3p, miR-139-5p, miR-378, miR-31, miR-195, miR-497 and miR-133b. Three of them, miR-139-5p, miR-497 and miR-768-3p, were first found in non-tumorous tissues. The most highly expressed miRNAs in gastric cancer tissues were miR-20b, miR-20a, miR-17, miR-106a, miR-18a, miR-21, miR-106b, miR-18b, miR-421, miR-340*, miR-19a and miR-658. Among them, miR-340*, miR-421 and miR-658 were first found highly expressed in cancer cells. The expression of some target genes (such as Rb and PTEN) in cancer tissues was found to be decreased. CONCLUSION: To our knowledge, this is the first report about these miRNAs associated with gastric cancer. This new information may suggest the potential roles of these miRNAs in the diagnosis of gastric cancer.
LinkOut: [PMID: 19175831]
Experimental Support 8 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method Luciferase reporter assay
Conditions MCF-7
Location of target site 3'UTR
Tools used in this research miRanda , PicTar , TargetScan
Original Description (Extracted from the article) ... Phosphatase and tensin homolog (PTEN) was discovered as a potential target of miR-21 through a bioinformatics approach. PTEN protein expression level was increased about two- to three-fold upon miR-21 inhibition in human hepatocellular carcinoma cells, while again there was no direct effect of miR-21 on PTEN mRNA abundance. ...

- Yang, Y. Chaerkady, R. Beer, M. A. Mendell, et al., 2009, Proteomics.

Article - Yang, Y. Chaerkady, R. Beer, M. A. Mendell, et al.
- Proteomics, 2009
MicroRNA (miRNA) play essential roles in biological processes ranging from cellular proliferation to apoptosis. Recently, miRNA have also been implicated in a number of diseases including cancers. However, the targets of most miRNA remain unknown. The majority of reports describing identification of miRNA targets are based on computational approaches or detection of altered mRNA levels despite the fact that most miRNA are thought to regulate their targets primarily at the level of translational inhibition in animals. miR-21 is a miRNA with oncogenic activity that is involved in various cancer-related processes such as invasion and migration. Given the importance of miR-21 in tumorigenesis, we employed a quantitative proteomic strategy to systematically identify potential targets of miR-21. By knocking down the expression of endogenous miR-21 in MCF-7 breast cancer cells, we observed an increase in the abundance of 58 proteins, implying that they could be potential targets of miR-21. Validation of 12 of these candidate targets in luciferase assays showed that 6 of them were likely direct targets of miR-21. Importantly, the mRNA of the majority of the candidate targets tested did not show a concomitant increase in abundance. Overall, our results demonstrate that miR-21 affects the expression of many of its targets through translational inhibition and highlights the utility of proteomic approaches for identifying miRNA targets.
LinkOut: [PMID: 19253296]
Experimental Support 9 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method Other
Article - Bethke, A. Fielenbach, N. Wang, Z. et al.
- Science, 2009
In response to small-molecule signals such as retinoids or steroids, nuclear receptors activate gene expression to regulate development in different tissues. MicroRNAs turn off target gene expression within cells by binding complementary regions in messenger RNA transcripts, and they have been broadly implicated in development and disease. Here we show that the Caenorhabditis elegans nuclear receptor DAF-12 and its steroidal ligand directly activate promoters of let-7 microRNA family members to down-regulate the microRNA target hbl-1, which drives progression of epidermal stem cells from second to third larval stage patterns of cell division. Conversely, the receptor without the ligand represses microRNA expression during developmental arrest. These findings identify microRNAs as components of a hormone-coupled molecular switch that shuts off earlier developmental programs to allow for later ones.
LinkOut: [PMID: 19342589]
Experimental Support 10 for Non-Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Non-Functional MTI ]
Validation Method Immunohistochemistry
Conditions Flat epithelial atypia sections
Location of target site NCR
Original Description (Extracted from the article) ... Immunohistochemical staining for PTEN revealed no obvious changes in staining intensities in normal, FEA, DCIS and IDC. ...

- Qi, L. Bart, J. Tan, L. P. Platteel, I. et al., 2009, BMC Cancer.

Article - Qi, L. Bart, J. Tan, L. P. Platteel, I. et al.
- BMC Cancer, 2009
BACKGROUND: Flat epithelial atypia (FEA) of the breast is characterised by a few layers of mildly atypical luminal epithelial cells. Genetic changes found in ductal carcinoma in situ (DCIS) and invasive ductal breast cancer (IDC) are also found in FEA, albeit at a lower concentration. So far, miRNA expression changes associated with invasive breast cancer, like miR-21, have not been studied in FEA. METHODS: We performed miRNA in-situ hybridization (ISH) on 15 cases with simultaneous presence of normal breast tissue, FEA and/or DCIS and 17 additional cases with IDC. Expression of the miR-21 targets PDCD4, TM1 and PTEN was investigated by immunohistochemistry. RESULTS: Two out of fifteen cases showed positive staining for miR-21 in normal breast ductal epithelium, seven out of fifteen cases were positive in the FEA component and nine out of twelve cases were positive in the DCIS component. A positive staining of miR-21 was observed in 15 of 17 IDC cases. In 12 cases all three components were present in one tissue block and an increase of miR-21 from normal breast to FEA and to DCIS was observed in five cases. In three cases the FEA component was negative, whereas the DCIS component was positive for miR-21. In three other cases, normal, FEA and DCIS components were negative for miR-21 and in the last case all three components were positive. Overall we observed a gradual increase in percentage of miR-21 positive cases from normal, to FEA, DCIS and IDC. Immunohistochemical staining for PTEN revealed no obvious changes in staining intensities in normal, FEA, DCIS and IDC. Cytoplasmic staining of PDCD4 increased from normal to IDC, whereas, the nuclear staining decreased. TM1 staining decreased from positive in normal breast to negative in most DCIS and IDC cases. In FEA, the staining pattern for TM1 was similar to normal breast tissue. CONCLUSION: Upregulation of miR-21 from normal ductal epithelial cells of the breast to FEA, DCIS and IDC parallels morphologically defined carcinogenesis. No clear relation was observed between the staining pattern of miR-21 and its previously reported target genes.
LinkOut: [PMID: 19473551]
Experimental Support 11 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method GFP reporter assay , Northern blot , qRT-PCR , Western blot , ASO assay
Conditions KAI , NKL , MOTN1
Location of target site 3'UTR
Original Description (Extracted from the article) ... Apoptotic activity was diminished in MOTN1 cells transduced with miR-21 whereas Western analysis showed that levels of PTEN and PDCD4 were reduced and those of pAKT were increased in the transductant cells.//ASO-21 and ASO-155, which reduced expression of both miR-21 and miR-155, levels of PTEN and SHIP1 were increased.//In addition, up-regulation PDCD4 was also detected. ...

- Yamanaka, Y. Tagawa, H. Takahashi, N. et al., 2009, Blood.

Article - Yamanaka, Y. Tagawa, H. Takahashi, N. et al.
- Blood, 2009
The gene(s) responsible for natural killer (NK)-cell lymphoma/leukemia have not been identified. In the present study, we found that in NK-cell lymphoma lines (n = 10) and specimens of primary lymphoma (n = 10), levels of miR-21 and miR-155 expression were inversely related and were significantly greater than those found in normal natural killer (CD3(-)CD56(+)) cells (n = 8). To determine the functions of these microRNAs in lymphomagenesis, we examined the effects of antisense oligonucleotides (ASOs) targeting miR-21 (ASO-21) and/or miR-155 (ASO-155) in NK-cell lymphoma lines overexpressing one or both of these miRNAs. Conversely, cells showing little endogenous expression of miR-21 or miR-155 were transduced by the use of lentiviral vectors, leading to their overexpression. Reducing expression of miR-21 or miR-155 led to up-regulation of phosphatase and tensin homologue (PTEN), programmed cell death 4 (PDCD4), or Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1). ASO-21- and ASO-155-treated cell lines all showed down-regulation of phosphorylated AKT(ser473). Moreover, transduction with either miR-21 or miR-155 led to down-regulation of PTEN and PDCD4 or SHIP1 with up-regulation of phosphorylated AKT(ser473). Collectively, these results provide important new insight into the pathogenesis of NK-cell lymphoma/leukemia and suggest targeting miR-21 and/or miR-155 may represent a useful approach to treating NK-cell lymphoma/leukemia.
LinkOut: [PMID: 19641183]
Experimental Support 12 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method Western blot , Other
Conditions Cholesteatoma and matched skin samples
Original Description (Extracted from the article) ... Western blot was used to compare levels of PTEN and PDCD-4 protein in cholesteatoma as compared with normal skin (Fig. 3). Expression of PTEN was reduced in 3 of 4 cholesteatoma samples. In 2 of these experiments, there was an absence of detectable PTEN in cholesteatoma. Similarly, cholesteatoma expression of PDCD-4 was also reduced in 3 of 4 patients when compared with matched normal skin controls. Absence of PDCD-4 was noted in 1 sample. ...

- Friedland, D. R. Eernisse, R. Erbe, C. et al., 2009, Otol Neurotol.

Article - Friedland, D. R. Eernisse, R. Erbe, C. et al.
- Otol Neurotol, 2009
OBJECTIVES:: The goal of this study was to identify novel regulatory mechanisms controlling the growth and proliferation of cholesteatoma. Specifically, the potential role of microRNAs, regulators of protein translation, was studied in cholesteatoma. STUDY DESIGN:: This study represents a molecular biologic investigation characterizing and comparing microRNA and protein expression in cholesteatoma and normal postauricular skin. METHODS:: Cholesteatoma and normal skin were taken from patients at the time of surgery. Tissue was processed for RNA and protein extraction. Real-time reverse-transcriptase-polymerase chain reaction was used to assess levels of human microRNAs, reverse-transcriptase-polymerase chain reaction was used to confirm the presence of upstream regulators, and Western blot analyses were used to assess levels of downstream target proteins. RESULTS:: Among the microRNAs investigated, human microRNA-21 (hsa-miR-21) showed a 4.4-fold higher expression in cholesteatoma as compared with normal skin (p = 0.0011). The downstream targets of hsa-miR-21, PTEN and programmed cell death 4, were found to be greatly reduced in 3 of 4 cholesteatoma samples. Proposed upstream regulators of hsa-miR-21 expression (CD14, interleukin 6R, gp130, and signal transducer and activator of transcription 3) were present in all cholesteatoma tissues. CONCLUSION:: MicroRNAs represent powerful regulators of protein translation, and their dysregulation has been implicated in many neoplastic diseases. This study specifically identified up-regulation of hsa-miR-21 concurrent with down-regulation of potent tumor suppressor proteins PTEN and programmed cell death 4. These proteins control aspects of apoptosis, proliferation, invasion, and migration. The results of this study were used to develop a model for cholesteatoma proliferation through microRNA dysregulation. This model can serve as a template for further study into potential RNA-based therapies for the treatment of cholesteatoma.
LinkOut: [PMID: 19672202]
Experimental Support 13 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method qRT-PCR , Western blot , Other
Conditions MSMC
Location of target site 3'UTR
Tools used in this research Literature survey , miRDB , TargetScan
Article - Pan, Q. Luo, X. Chegini, N.
- Mol Hum Reprod, 2010
Aberrant expression of microRNAs (miRNAs), including miR-21, and alteration of their target genes stability have been associated with cellular transformation and tumorigenesis. We investigated the expression, regulation and function of miR-21 in leiomyomas which develop from myometrial cellular transformation. The results indicated that miR-21 is over-expressed in leiomyomas with specific elevation during the secretory phase of the menstrual cycle and in women who received Depo-Provera and oral contraceptives, but reduced due to GnRHa therapy (P < 0.05). Bioinformatic analysis of microarray gene expression profiles previously obtained from the above cohorts, and myometrial smooth muscle cells (MSMC) and leiomyoma smooth muscle cells (LSMC) treated with GnRHa, transforming growth factor (TGF)-beta and TGF-beta receptor type II (TGF-betaRII) antisense oligomer, indicated that a number of miR-21-predicted target genes were co-expressed and differentially regulated in these cohorts. Gain- and loss-of-function of miR-21 in MSMC, LSMC, transformed LSMC and leiomyosarcoma cell line (SKLM-S1) resulted in differential expression of many genes, including some of the miR-21-predicted/validated target genes, PTEN, PDCD4 and E2F1, and TGF-betaRII, in a cell-specific manner. Gain-of miR-21 function in MSMC and LSMC reduced TGF-beta-induced expression of fibromodulin and TGF-beta-induced factor (P < 0.05), and moderately altered the rate of cell growth and caspase-3/7 activity in these cells. We concluded that miR-21 is aberrantly expressed and hormonally regulated in leiomyomas where, through functional interaction with ovarian steroids and the TGF-beta signaling pathway, either directly or indirectly regulates a number of genes whose products are critical in leiomyoma growth and regression as well as their potential cellular transformation.
LinkOut: [PMID: 19906824]
Experimental Support 14 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method Luciferase reporter assay , Western blot , Reporter assay;Western blot;Microarray
Conditions U251
Location of target site 3'UTR
Original Description (Extracted from the article) ... The results showed that the AS-miR-21 caused a four- to sixfold decrease in luciferase activity in pGL3-PTEN-3`UTR-transfected cells (Figure 4a and b). Thus, the miR-21 binding site in 3`UTR of PTEN gene is functional. ...

- Zhou, X. Ren, Y. Moore, L. Mei, M. You, Y. et al., 2010, Lab Invest.

Article - Zhou, X. Ren, Y. Moore, L. Mei, M. You, Y. et al.
- Lab Invest, 2010
MicroRNAs (miRNAs) are a class of endogenous small noncoding RNAs that regulate gene expression after transcription. Aberrant expression of miRNAs has been shown to be involved in tumorigenesis. We showed that miR-21 was one of the most frequently overexpressed miRNA in human glioblastoma (GBM) cell lines. To explore whether miR-21 can serve as a therapeutic target for glioblastoma, we downregulated miR-21 with a specific antisense oligonucleotide and found that apoptosis was induced and cell-cycle progression was inhibited in vitro in U251 (PTEN mutant) and LN229 (PTEN wild-type) GBM cells; xenograft tumors from antisense-treated U251 cells were suppressed in vivo. Antisense-miR-21-treated cells showed a decreased expression of EGFR, activated Akt, cyclin D, and Bcl-2. Although miR-21 is known to regulate PTEN and downregulation of miR-21 led to increased PTEN expression both endogenously and in a reporter gene assay, the GBM suppressor effect of antisense-miR-21 is most likely independent of PTEN regulation because U251 has mutant PTEN. Microarray analysis showed that the knockdown of miR-21 significantly altered expression of 169 genes involved in nine cell-cycle and signaling pathways. Taken together, our studies provide evidence that miR-21 may serve as a novel therapeutic target for malignant gliomas independent of PTEN status.
LinkOut: [PMID: 20048743]
Experimental Support 15 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method Western blot
Location of target site 3'UTR
Article - Inui, M. Martello, G. Piccolo, S.
- Nat Rev Mol Cell Biol, 2010
MicroRNAs (miRNAs) are integral elements in the post-transcriptional control of gene expression. After the identification of hundreds of miRNAs, the challenge is now to understand their specific biological function. Signalling pathways are ideal candidates for miRNA-mediated regulation owing to the sharp dose-sensitive nature of their effects. Indeed, emerging evidence suggests that miRNAs affect the responsiveness of cells to signalling molecules such as transforming growth factor-beta, WNT, Notch and epidermal growth factor. As such, miRNAs serve as nodes of signalling networks that ensure homeostasis and regulate cancer, metastasis, fibrosis and stem cell biology.
LinkOut: [PMID: 20216554]
Experimental Support 16 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method qRT-PCR , Luciferase reporter assay , Western blot
Conditions A549 , H1703
Location of target site 3'UTR
Original Description (Extracted from the article) ... Tumor tissues showed an inverse correlation between miR-21 and PTEN protein. miR-21 inhibitor transfection increased a luciferase-reporter activity containing the PTEN-3′-UTR construct and increased PTEN protein but not PTEN-mRNA levels in NSCLC cell lines. Finally, miR-21 inhibitor-transfected cells exhibited markedly reduced cell growth and invasive characteristics.//miR-21 post-transcriptionally down-regulates the expression of tumor suppressor PTEN and stimulates growth and invasion in NSCLC.//PTEN is a direct target of miR-21//However, the mutant reporter plasmid abolished miR-21 inhibitor-mediated increase in luciferase activity (Fig. 3B). These findings suggest that miR-21 suppresses PTEN by direct binding to the 3′-UTR of PTEN. ...

- Zhang, J. G. Wang, J. J. Zhao, F. Liu, Q. et al., 2010, Clin Chim Acta.

miRNA-target interactions (Provided by authors)
IDDuplex structurePosition
1
miRNA  3' agUUGUAGUCAGACUAUUCGAu 5'
            ::|| ||    ||||||:| 
Target 5' guGGCAACA----GAUAAGUUu 3'
5 - 22
Article - Zhang, J. G. Wang, J. J. Zhao, F. Liu, Q. et al.
- Clin Chim Acta, 2010
BACKGROUND: MicroRNAs (miRNAs) are a class of small non-coding RNAs regulating gene expression that play roles in the pathogenesis of human diseases, including malignancy. miR-21, a commonly overexpressed miRNA in very diverse types of malignancies, may affect tumor progression through targeting tumor suppressor genes. We identified the role of miR-21 in non-small cell lung cancer (NSCLC) and to clarify the regulation of PTEN by miR-21 and determine mechanisms of this regulation. METHODS: Expression of miR-21 and PTEN in 20 paired NSCLC and adjacent non-tumor lung tissues was investigated by qRT-PCR and western blot, respectively. The effect of miR-21 on PTEN expression was assessed in NSCLC cell lines with miR-21 inhibitor to decrease miR-21 expression. Furthermore, the roles of miR-21 in cell growth and invasion were analyzed with miR-21 inhibitor-transfected cells. RESULTS: miR-21 was overexpressed in tumor tissues relative to adjacent non-tumor tissues. Notably, patients with advanced clinical TNM stage (n=16) or distal metastasis (n=5) demonstrat- ed higher miR-21 expression than those without them (n=26, or n=37) (p<0.05, or p<0.001). Tumor tissues showed an inverse correlation between miR-21 and PTEN protein. miR-21 inhibit- or transfection increased a luciferase-reporter activity containing the PTEN-3(')-UTR construct and increased PTEN protein but not PTEN mRNA levels in NSCLC cell lines. Finally, miR-21 inhibitor-transfected cells exhibited markedly reduced cell growth and invasive characteristics. CONCLUSIONS: miR-21 post-transcriptionally down-regulates the expression of tumor suppressor PTEN and stimulates growth and invasion in NSCLC. It may be a potential therapeutic target for NSCLC.
LinkOut: [PMID: 20223231]
Experimental Support 17 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method Luciferase reporter assay , qRT-PCR
Conditions MCF10A , HCT116 , HT29 , PC3 , A549 , HeLa , Hep 3B , PANC1
Location of target site 3'UTR
Tools used in this research Unspecified
Original Description (Extracted from the article) ... miR-21 targets directly PTEN tumor suppressor gene// miR-21 and miR-181b-1,respectively, inhibit PTEN and CYLD tumor suppressors, leading to increased NF-kB activity required to maintain the transformed state ...

- Iliopoulos, D. Jaeger, S. A. Hirsch, H. A. et al., 2010, Mol Cell.

Article - Iliopoulos, D. Jaeger, S. A. Hirsch, H. A. et al.
- Mol Cell, 2010
A transient inflammatory signal can initiate an epigenetic switch from nontransformed to cancer cells via a positive feedback loop involving NF-kappaB, Lin28, let-7, and IL-6. We identify differentially regulated microRNAs important for this switch and putative transcription factor binding sites in their promoters. STAT3, a transcription factor activated by IL-6, directly activates miR-21 and miR-181b-1. Remarkably, transient expression of either microRNA induces the epigenetic switch. MiR-21 and miR-181b-1, respectively, inhibit PTEN and CYLD tumor suppressors, leading to increased NF-kappaB activity required to maintain the transformed state. These STAT3-mediated regulatory circuits are required for the transformed state in diverse cell lines and tumor growth in xenografts, and their transcriptional signatures are observed in colon adenocarcinomas. Thus, STAT3 is not only a downstream target of IL-6 but, with miR-21, miR-181b-1, PTEN, and CYLD, is part of the positive feedback loop that underlies the epigenetic switch that links inflammation to cancer.
LinkOut: [PMID: 20797623]
Experimental Support 18 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method qRT-PCR , Western blot
Conditions BxPC3 , DU145
Location of target site 3'UTR
Original Description (Extracted from the article) ... PTEN is upregulated in miR-21 knockdown cells, suggesting that PTEN is a target of miR-21 in DU145 cells. ...

- Yang, C. H. Yue, J. Fan, M. Pfeffer, L. M., 2010, Cancer Res.

Article - Yang, C. H. Yue, J. Fan, M. Pfeffer, L. M.
- Cancer Res, 2010
The microRNA miR-21 is overexpressed in many human cancers, wherein accumulating evidence indicates that it functions as an oncogene. Here, we report that the cytokine IFN rapidly induces miR-21 expression in human and mouse cells. Signal transducer and activator of transcription 3 (STAT3) was implicated in this pathway based on the lack of IFN effect on miR-21 expression in prostate cancer cells with a deletion in the STAT3 gene. STAT3 ablation abrogated IFN induction of miR-21, confirming the important role of STAT3 in regulating miR-21. Chromatin immunoprecipitation analysis showed that STAT3 directly bound the miR-21 promoter in response to IFN. Experiments in mouse embryo fibroblasts with a genetic deletion of the p65 NF-kappaB subunit showed that IFN-induced miR-21 expression was also dependent on NF-kappaB. STAT3 silencing blocked both IFN-induced p65 binding to the miR-21 promoter and p65 nuclear translocation. Thus, IFN-induced miR-21 expression is coregulated by STAT3 and NF-kappaB at the level of the miR-21 promoter. Several cell death regulators were identified as downstream targets of miR-21, including PTEN and Akt. Functional experiments in prostate cancer cells directly showed that miR-21 plays a critical role in suppressing IFN-induced apoptosis. Our results identify miR-21 as a novel IFN target gene that functions as a key feedback regulator of IFN-induced apoptosis.
LinkOut: [PMID: 20813833]
Experimental Support 19 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method Immunohistochemistry , qRT-PCR , Western blot
Conditions PLC/PRF/5 , HuH7 , HLE , HLF , Hep G2
Disease hepatocellular carcinoma
Location of target site 3'UTR
Tools used in this research Unspecified
Original Description (Extracted from the article) ... The expression levels of PTEN and PDCD4 tended to correlate inversely with that of miR-21 in tumour tissues ...

- Tomimaru, Y. Eguchi, H. Nagano, H. Wada, H. et al., 2010, Br J Cancer.

Article - Tomimaru, Y. Eguchi, H. Nagano, H. Wada, H. et al.
- Br J Cancer, 2010
Background:We reported recently the clinical efficiency of interferon (IFN)-alpha/5-fluorouracil (5-FU) combination therapy in advanced hepatocellular carcinoma (HCC). However, prediction of the response to the combination therapy remains unsatisfactory. The aim of this study was to investigate the anti-tumour effects of microRNA (miR)-21 on the sensitivity of HCC cells to IFN-alpha/5-FU and whether miR-21 can be used as a predictor of the response to such therapy in HCC.Methods:Changes in the sensitivity of HCC cells (PLC/PRF/5 and HepG2) to IFN-alpha/5-FU were examined after transfection with pre-miR-21 or anti-miR-21. The correlation between miR-21 expression level, evaluated by qRT-PCR, and response to the therapy was also investigated in clinical HCC specimens.Results:Hepatocellular carcinoma cells transfected with pre-miR-21 were significantly resistant to IFN-alpha/5-FU. Annexin V assay showed that the percentage of apoptotic cells was significantly lower in cells transfected with pre-miR-21 than control cells. Transfection of anti-miR-21 rendered HCC cells sensitive to IFN-alpha/5-FU, and such sensitivity was weakened by transfection of siRNAs of target molecules, PETN and PDCD4. miR-21 expression in clinical HCC specimens was significantly associated with the clinical response to the IFN-alpha/5-FU combination therapy and survival rate.Conclusions:The miR-21 in HCC cell lines and clinical HCC samples is a significant modulator of the anti-tumour effect of IFN-alpha and 5-FU. This suggests that miR-21 is a potentially suitable marker for the prediction of the clinical response to the IFN-alpha/5-FU combination therapy.British Journal of Cancer advance online publication, 26 October 2010; doi:10.1038/sj.bjc.6605958 www.bjcancer.com.
LinkOut: [PMID: 20978511]
Experimental Support 20 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method Luciferase reporter assay , Microarray , Northern blot , qRT-PCR , Western blot
Conditions K562
Location of target site 3'UTR
Tools used in this research miRBase Target Database
Original Description (Extracted from the article) ... Our results show that leukaemia cells with elevated miR-21 expression and decreased PTEN protein expression were more resistant to DNR than the control cells. These results may help with the development of personalized treatment for patients who have abnormal levels of miR-21 or PTEN. ...

- Bai, H. Xu, R. Cao, Z. Wei, D. Wang, C., 2011, FEBS letters.

Article - Bai, H. Xu, R. Cao, Z. Wei, D. Wang, C.
- FEBS letters, 2011
Recent studies have shown microRNA-21 (miR-21) is overexpressed in several types of cancer and contributes to tumor resistance to chemotherapy. In this study, we investigated whether miR-21 mediated resistance of the leukaemia cell line K562 to the chemotherapeutic agent daunorubicin (DNR). miR-21 expression was upregulated in the DNR resistant cell line K562/DNR compared to its parental line K562. Stable transfection of miR-21 induced drug resistance in K562, while suppression of miR-21 in K562/DNR led to enhanced DNR cytotoxicity. Additional experiments indicate that the mechanism of miR-21 drug resistance involves the PI3K/Akt pathway and changes following PTEN protein expression. This study provides a novel mechanism for understanding leukaemia drug resistance.
LinkOut: [PMID: 21187093]
Experimental Support 21 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method Western blot
Article - Liu, L. Z. Li, C. Chen, Q. Jing, Y. et al.
- PLoS One, 2011
MicroRNAs (miRNAs) are endogenous, small noncoding RNAs that play important roles in various cellular functions and tumor development. Recent studies have indicated that miR-21 is one of the important miRNAs associated with tumor growth and metastasis, but the role and molecular mechanism of miR-21 in regulating tumor angiogenesis remain to be elucidated. In this study, miR-21 was overexpressed by transfecting pre-miR-21 into human prostate cancer cells and tumor angiogenesis was assayed using chicken chorioallantoic membrane (CAM). We found that overexpression of miR-21 in DU145 cells increased the expression of HIF-1alpha and VEGF, and induced tumor angiogenesis. AKT and extracellular regulated kinases (ERK) 1/2 are activated by miR-21. Inhibition of miR-21 by the antigomir blocked this process. Overexpression of the miR-21 target, PTEN, also inhibited tumor angiogenesis by partially inactivating AKT and ERK and decreasing the expression of HIF-1 and VEGF. The AKT and ERK inhibitors, LY294002 and U0126, suppressed HIF-1alpha and VEGF expression and angiogenesis. Moreover, inhibition of HIF-1alpha expression alone abolished miR-21-inducing tumor angiogenesis, indicating that HIF-1alpha is required for miR-21-upregulated angiogenesis. Therefore, we demonstrate that miR-21 induces tumor angiogenesis through targeting PTEN, leading to activate AKT and ERK1/2 signaling pathways, and thereby enhancing HIF-1alpha and VEGF expression; HIF-1alpha is a key downstream target of miR-21 in regulating tumor angiogenesis.
LinkOut: [PMID: 21544242]
Experimental Support 22 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method Luciferase reporter assay , qRT-PCR , Western blot
Conditions MCF-7
Disease breast cancer
Location of target site 3'UTR
Tools used in this research miRBase Target Database , TargetScan
Original Description (Extracted from the article) ... Upregulation of miR-21 and downregulation of PTEN may be involved in ADR-resistant phenotype of breast cancer cells//PTEN is target of miR-21 ...

- Wang, Z. X. Lu, B. B. Wang, H. Cheng, Z. X. et al., 2011, Arch Med Res.

Article - Wang, Z. X. Lu, B. B. Wang, H. Cheng, Z. X. et al.
- Arch Med Res, 2011
BACKGROUND AND AIMS: Ovexpression of microRNA-21 (miR-21) is found in various human cancers. Our aim is to investigate the association of miR-21 expression with the sensitivity of breast cancer cells to doxorubicin (ADR). METHODS: The half maximal inhibitory concentration (IC(50)) value of ADR in resistant MCF-7/ADR or parental MCF-7 cells was determined by MTT assay. TaqMan RT-PCR or Western blot assay was performed to detect the expression of mature miR-21 and tumor suppressor gene (PTEN) protein. MCF-7 or MCF-7/ADR cell line was transfected with miR-21mimic or inhibitor. The IC(50) value of ADR was determined. Flow cytometry and TUNEL assays were performed to analyze apoptosis. The activity of caspase-3 was analyzed. RESULTS: The IC(50) of ADR in MCF-7 and MCF-7/ADR cells was 0.21 +/- 0.05 and 16.5 +/- 0.08 mumol/L, respectively. We showed that upregulation of miR-21 in MCF-7/ADR cells was concurrent with downregulation of PTEN protein. MiR-21 mimic or inhibitor could obviously affect the sensitivity of breast cancer cells to ADR. Moreover, miR-21 inhibitor could enhance caspase-3-dependent apoptosis in MCF-7/ADR cells. Overexpression of PTEN could mimic the same effects of miR-21 inhibitor in MCF-7/ADR cells and PTEN-siRNA could increase the resistance of MCF-7 cells to ADR. MiR-21 inhibitor could increase PTEN protein expression and the luciferase activity of a PTEN 3' untranslated region-based reporter construct in MCF-7/ADR cells. PTEN-siRNA could partially reverse the increased chemosensitivity of MCF-7/ADR cells induced by miR-21 inhibitor. CONCLUSIONS: Dysregulation of miR-21 plays critical roles in the ADR resistance of breast cancer, at least in part via targeting PTEN.
LinkOut: [PMID: 21820606]
Experimental Support 23 for Non-Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Non-Functional MTI ]
Validation Method Luciferase reporter assay , Western blot
Conditions SGC-7901 , MKN-28 , MKN-45AGS , NCI-N87 , BGC-823 , HTB-103 , CRL-5974 , CRL-5971 , GES-1
Disease gastric cancer
Location of target site 3'UTR
Original Description (Extracted from the article) ... these results indicate that PTEN-3'-UTR carries the direct binding sites of miR-21 not affect luciferase activity controlled by mutant PTEN-3'-UTR ...

- Zhang, B. G. Li, J. F. Yu, B. Q. Zhu, Z. G. et al., 2012, Oncol Rep.

Article - Zhang, B. G. Li, J. F. Yu, B. Q. Zhu, Z. G. et al.
- Oncol Rep, 2012
Gastric cancer is one of the most common carcinomas in China. microRNAs, a type of non-coding RNA, are important specific regulators and are involved in numerous bioprocesses of an organism. microRNA-21 (miR-21) has been identified as the most suitable choice for further investigation because it is overexpressed in nearly all solid tumors; furthermore, it has been demonstrated that miR-21 is involved in the genesis and progression of human cancer. It has been reported that PTEN, an important tumour suppressor, is regulated by multiple miRNAs. Thus, in this study we focused on the expression and significance of miR-21 in gastric cancer tissues, and the role of miR-21 in the biological behaviour and the expression of PTEN in gastric cancer cells. Real-time PCR was used to detect miR-21 expression in gastric cancer tissues, the adjacent normal tissues, and the gastric cell lines. The gastric cancer cell line BGC-823 was transfected with pre-miR-21/miR-21 inhibitor to overexpress/downregulate miR-21. The influence of miR-21 on the biological behaviour of gastric cancer cells was evaluated using the CCK-8 kit, FCMs, the scratch healing assay and the transwell test. Western blotting and the Luciferase Reporter Assay were used to evaluate the change of PTEN expression after lowered expression of miR-21 in gastric cancer cell lines. Real-time PCR analysis indicated that miR-21 exhibited higher expression in gastric cancer tissues compared to the adjacent non-tumor tissues. miR-21 expression was significantly associated with the degree of differentiation of the tumour tissues (P=0.004), as well as local invasion and lymph node metastasis (P<0.01). After transfection, pre-miR21 BGC-823 cells grew faster than the negative and control groups (P<0.01). The reduction in miR-21 expression demonstrated a remarkable effect on the biological behaviour of gastric cancer cells (P<0.05); the pre-miR-21-transfected cells healed more quickly compared to the control cells in the scratch healing assay, whereas the transwell test indicated that cell migration in vitro was notably inhibited with the downregulation of miR-21 (P<0.05). The western blot results and Luciferase Reporter Assay demonstrated that PTEN expression was remarkably increased after miR-21 inhibition (P<0.05). microRNA-21 expression was upregulated in gastric carcinoma tissues and was significantly associated with the degree of differentiation of tumour tissues, local invasion and lymph node metastasis. Overexpression of miR-21 promoted BGC-823 cell growth, invasion and cell migration in vitro, whereas downregulation of miR-21 exhibited a stronger inhibitory effect on the biological behaviour of gastric cancer cells; additionally, miR-21 inhibition may upregulate the PTEN expression level, which indicates that PTEN may be a target gene for gastric cancer initiation and development.
LinkOut: [PMID: 22267008]
Experimental Support 24 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method ELISA , Immunoblot , qRT-PCR
Conditions MCF 10A , MDA-MB-231 , MCF-7
Location of target site 3'UTR
Original Description (Extracted from the article) ... miR-21 targeted the PTEN 3′-UTR directly in these cells ...

- Mandal, C. C. Ghosh-Choudhury, T. Dey, N. et al., 2012, Carcinogenesis.

Article - Mandal, C. C. Ghosh-Choudhury, T. Dey, N. et al.
- Carcinogenesis, 2012
Increasing evidence shows the beneficial effects of fish oil on breast cancer growth and invasion in vitro and in animal models. Expression of CSF-1 (colony stimulating factor-1) by breast cancer cells acts as potent activator of malignancy and metastasis. In this report, we used two human breast cancer cell lines, MDA-MB-231 and MCF-7, to show that the bioactive fish oil component DHA (docosahexaenoic acid) inhibits expression of CSF-1 and its secretion from these cancer cells. We found that the tumor suppressor protein PTEN regulates CSF-1 expression through PI 3 kinase/Akt signaling via a transcriptional mechanism. The enhanced abundance of microRNA-21 (miR-21) in breast cancer cells contributes to the growth and metastasis. Interestingly, DHA significantly inhibited expression of miR-21. miR-21 Sponge, which derepresses the miR-21 targets, markedly decreased expression of CSF-1 and its secretion. Furthermore, miR-21-induced upregulation of CSF-1 mRNA and its transcription were prevented by expression of PTEN mRNA lacking 3'-untranslated region (UTR) and miR-21 recognition sequence. Strikingly, miR-21 reversed DHA-forced reduction of CSF-1 expression and secretion. Finally, we found that expression of miR-21 as well as CSF-1 was significantly attenuated in breast tumors of mice receiving a diet supplemented with fish oil. Our results reveal a novel mechanism for the therapeutic function of fish oil diet that blocks miR-21, thereby increasing PTEN levels to prevent expression of CSF-1 in breast cancer.
LinkOut: [PMID: 22678116]
Experimental Support 25 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method qRT-PCR , Western blot
Conditions MDA-MB-231
Original Description (Extracted from the article) ... MiR-21 Targeted PTEN in Reversing EMT and CSC Phenotype ...

- Han, M. Liu, M. Wang, Y. Chen, X. Xu, J. et al., 2012, PLoS One.

Article - Han, M. Liu, M. Wang, Y. Chen, X. Xu, J. et al.
- PLoS One, 2012
BACKGROUND: Accumulating evidence suggested that epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) characteristics, both of which contribute to tumor invasion and metastasis, are interrelated with miR-21. MiR-21 is one of the important microRNAs associated with tumor progression and metastasis, but the molecular mechanisms underlying EMT and CSC phenotype during miR-21 contributes to migration and invasion of breast cancer cells remain to be elucidated. METHODOLOGY/PRINCIPAL FINDINGS: In this study, MDA-MB-231/anti-miR-21 cells were established by transfected hsa-miR-21 antagomir into breast cancer MDA-MB-231 cells. EMT was evaluated by the changes of mesenchymal cell markers (N-cadherin, Vimentin, and alpha-SMA), epithelial cell marker (E-cadherin), as well as capacities of cell migration and invasion; CSC phenotype was measured using the changes of CSC surface markers (ALDH1 and CD44), and the capacity of sphereforming (mammospheres). We found that antagonism of miR-21 reversed EMT and CSC phenotype, accompanied with PTEN up-regulation and AKT/ERK1/2 inactivation. Interestingly, down-regulation of PTEN by siPTEN suppressed the effects of miR-21 antagomir on EMT and CSC phenotype, confirming that PTEN is a target of miR-21 in reversing EMT and CSC phenotype. The inhibitors of PI3K-AKT and ERK1/2 pathways, LY294002 and U0126, both significantly suppressed EMT and CSC phenotype, indicating that AKT and ERK1/2 pathways are required for miR-21 mediating EMT and CSC phenotype. CONCLUSIONS/SIGNIFICANCE: In conclusion, our results demonstrated that antagonism of miR-21 reverses EMT and CSC phenotype through targeting PTEN, via inactivation of AKT and ERK1/2 pathways, and showed a novel mechanism of which might relieve the malignant biological behaviors of breast cancer.
LinkOut: [PMID: 22761812]
Experimental Support 26 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method Immunohistochemistry , Luciferase reporter assay , qRT-PCR , Western blot
Conditions 293A , CCA
Location of target site 3'UTR
Original Description (Extracted from the article) ... microRNA-21 expression is up-regulated in human cholangiocarcinoma and PTEN, PDCD4 are direct effectors of microRNA-21. ...

- Liu, C. Z. Liu, W. Zheng, Y. Su, J. M. Li, et al., 2012, Chin Med Sci J.

Article - Liu, C. Z. Liu, W. Zheng, Y. Su, J. M. Li, et al.
- Chin Med Sci J, 2012
OBJECTIVE: To investigate the expression profile of microRNA-21 in human cholangiocarcinoma tissues and to validate its bona fide targets in human cholangiocarcinoma cells. METHODS: The expression profile of microRNA-21 in human cholangiocarcinoma tissues and cholangiocarcinoma cell line, QBC939, was evaluated by using real-time PCR analysis. The bona fide targets of microRNA-21 were analyzed and confirmed by dual luciferase reporter gene assay and western blot, respectively. The expressional correlation of microRNA-21 and its targets was probed in human cholangiocarcinoma tissues by using real-time PCR, locked nucleic acid in situ hybridization (LNA-ISH), and immunohistochemistry analysis. RESULTS: Real-time PCR analysis revealed that microRNA-21 expression depicted a significant up-regulation in human cholangiocarcinoma tissues about 5.6-fold as compared to the matched normal bile duct tissues (P<0.05). The dual luciferase reporter gene assay revealed endogenous microRNA-21 in cholangiocarcinoma cell line, QBC939, inhibited the luciferase reporter activities of wild-type PTEN (P<0.01) and PDCD4 (P<0.05) and had no this effect on mutated PTEN and PDCD4. Moreover, loss of microRNA-21 function led to a significant increase of PTEN and PDCD4 protein levels in QBC939 cells. Elevated microRNA-21 levels were accompanied by marked reductions of PTEN and PDCD4 expression in the same cholangiocarcinoma tissue. CONCLUSION: microRNA-21 expression is up-regulated in human cholangiocarcinoma and PTEN, PDCD4 are direct effectors of microRNA-21.
LinkOut: [PMID: 22770403]
Experimental Support 27 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method Luciferase reporter assay , Western blot
Conditions Human glomerular mesangial cell , HEK293
Location of target site 3'UTR
Original Description (Extracted from the article) ... TGFb-stimulated miR-21 targets PTEN 39UTR to inhibit PTEN expression. ...

- Dey, N. Ghosh-Choudhury, N. Kasinath, B. S. et al., 2012, PLoS One.

Article - Dey, N. Ghosh-Choudhury, N. Kasinath, B. S. et al.
- PLoS One, 2012
Transforming growth factor-beta (TGFbeta) promotes glomerular hypertrophy and matrix expansion, leading to glomerulosclerosis. MicroRNAs are well suited to promote fibrosis because they can repress gene expression, which negatively regulate the fibrotic process. Recent cellular and animal studies have revealed enhanced expression of microRNA, miR-21, in renal cells in response to TGFbeta. Specific miR-21 targets downstream of TGFbeta receptor activation that control cell hypertrophy and matrix protein expression have not been studied. Using 3'UTR-driven luciferase reporter, we identified the tumor suppressor protein PTEN as a target of TGFbeta-stimulated miR-21 in glomerular mesangial cells. Expression of miR-21 Sponge, which quenches endogenous miR-21 levels, reversed TGFbeta-induced suppression of PTEN. Additionally, miR-21 Sponge inhibited TGFbeta-stimulated phosphorylation of Akt kinase, resulting in attenuation of phosphorylation of its substrate GSK3beta. Tuberin and PRAS40, two other Akt substrates, and endogenous inhibitors of mTORC1, regulate mesangial cell hypertrophy. Neutralization of endogenous miR-21 abrogated TGFbeta-stimulated phosphorylation of tuberin and PRAS40, leading to inhibition of phosphorylation of S6 kinase, mTOR and 4EBP-1. Moreover, downregulation of miR-21 significantly suppressed TGFbeta-induced protein synthesis and hypertrophy, which were reversed by siRNA-targeted inhibition of PTEN expression. Similarly, expression of constitutively active Akt kinase reversed the miR-21 Sponge-mediated inhibition of TGFbeta-induced protein synthesis and hypertrophy. Furthermore, expression of constitutively active mTORC1 prevented the miR-21 Sponge-induced suppression of mesangial cell protein synthesis and hypertrophy by TGFbeta. Finally, we show that miR-21 Sponge inhibited TGFbeta-stimulated fibronectin and collagen expression. Suppression of PTEN expression and expression of both constitutively active Akt kinase and mTORC1 independently reversed this miR-21-mediated inhibition of TGFbeta-induced fibronectin and collagen expression. Our results uncover an essential role of TGFbeta-induced expression of miR-21, which targets PTEN to initiate a non-canonical signaling circuit involving Akt/mTORC1 axis for mesangial cell hypertrophy and matrix protein synthesis.
LinkOut: [PMID: 22879939]
Experimental Support 28 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method Luciferase reporter assay
Conditions SPC-A1 , A549 , H2170 , 16HBE
Location of target site 3'UTR
Tools used in this research miRBase Target Database , TargetScan
Original Description (Extracted from the article) ... PTEN was a functional and direct target of miR-21 ...

- Liu, Z. L. Wang, H. Liu, J. Wang, Z. X., 2012, Mol Cell Biochem.

Article - Liu, Z. L. Wang, H. Liu, J. Wang, Z. X.
- Mol Cell Biochem, 2012
MicroRNAs (miRNAs) regulate gene expression by binding to target sites and initiating translational repression and/or mRNA degradation. In our previous study, we have shown that expression of serum microRNA (miR)-21 is correlated with TNM stage and lymph node metastasis and might be an independent prognostic factor for NSCLC patients. However, the roles of miR-21 overexpression in NSCLC development are still unclear. The purpose of this study is to investigate the effect of miR-21 and determine whether miR-21 can be a therapeutic target for human NSCLC. Taqman real-time quantitative RT-PCR assay was performed to detect miR-21 expression in NSCLC cell lines and tissues. Next, the effects of miR-21 expression on NSCLC cell characteristics including growth, invasion, and chemo- or radioresistance were also determined. Results showed that miR-21 is commonly upregulated in NSCLC cell lines and tissues with important functional consequences. In addition, we found that anti-miR-21 could significantly inhibit growth, migration and invasion, and reverse chemo- or radioresistance of NSCLC cells, while miR-21 mimics could increase growth, promote migration and invasion, and enhance chemo- or radioresistance of NSCLC cells. Meanwhile, miR-21 mimics could inhibit expression of PTEN mRNA and protein and the luciferase activity of a PTEN 3'-untranslated region (UTR)-based reporter construct in A549 cells, while anti-miR-21 could increase expression of PTEN mRNA and protein and the luciferase activity of a PTEN 3'-UTR-based reporter construct in A549 cells. Furthermore, overexpression of PTEN could mimic the same effects of anti-miR-21 in NSCLC cells, and siRNA-mediated downregulation of PTEN could rescue the effects on NSCLC cells induced by anti-miR-21. Taken together, these results provide evidence to show the promotion role of miR-21 in NSCLC development through modulation of the PTEN signaling pathway.
LinkOut: [PMID: 22956424]
Experimental Support 29 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-21-5p :: PTEN    [ Functional MTI ]
Validation Method Luciferase reporter assay
Conditions KLE
Location of target site 3'UTR
Tools used in this research RNA22
Original Description (Extracted from the article) ... miR-21 directly targets the 3'-UTR of PTEN mRNA ...

- Qin, X. Yan, L. Zhao, X. Li, C. Fu, Y., 2012, Oncol Lett.

Article - Qin, X. Yan, L. Zhao, X. Li, C. Fu, Y.
- Oncol Lett, 2012
The aim of this study was to investigate the role of microRNA-21 (miR-21) in the regulation of phosphatase and tensin homolog deleted from chromosome-10 (PTEN) expression and proliferation of endometrioid endometrial cancer (EEC) cells. We performed a qRT-PCR assay with miR-21 and PTEN in 16 paired EEC tumor tissues and adjacent non-tumor endometrium. To investigate the regulation of PTEN by miR-21, we designed gain- and loss-of-function of miR-21 experiments in the KLE cell line by transfection with a synthetic miR-21 mimic and inhibitor. To validate the putative binding site of miR-21 in the 3' untranslated region (3'-UTR) of PTEN messenger RNA (mRNA), a dual-luciferase reporter assay was carried out. To evaluate the potential effect of miR-21 on EEC proliferation, we performed both overexpression experiments, using an miR-21 mimic, and inhibition assays, using an miR-21 inhibitor. miR-21 was overexpressed in EEC and was inversely correlated with PTEN protein expression (P<0.001). miR-21 regulated PTEN protein expression and cell proliferation in the KLE cell line and the direct binding of miR-21 to the PTEN 3'-UTR was confirmed using a dual-luciferase reporter assay. The upregulation of miR-21 led to a significant decrease in the PTEN protein expression level (P=0.007). The downregulation of miR-21 led to a significant increase in PTEN protein (P=0.002). The expression of luciferase in the wt-PTEN-3'-UTR-pGL3 group was downregulated in the presence of the miR-21 mimic (P=0.001). miR-21 was overexpressed in EEC. In conclusion, we demonstrated that the expression of PTEN protein, but not mRNA, was negatively directly regulated by miR-21 in the KLE cell line. The overexpression of miR-21 modulated EEC cell proliferation through the downregulation of PTEN.
LinkOut: [PMID: 23226804]
MiRNA-Target Expression Profile:

 
MiRNA-Target Interaction Network:
Strong evidence (reporter assay, western blot, qRT-PCR or qPCR)
Other evidence
525 hsa-miR-21-5p Target Genes:
ID Target Description Validation methods
Strong evidence Less strong evidence
MIRT000019 RASGRP1 RAS guanyl releasing protein 1 (calcium and DAG-regulated) 5 3
MIRT000157 CDC25A cell division cycle 25 homolog A (S. pombe) 4 3
MIRT000158 TP53 tumor protein p53 1 1
MIRT000159 BCL2 B-cell CLL/lymphoma 2 4 8
MIRT000163 WIBG within bgcn homolog (Drosophila) 1 2
MIRT000164 WFS1 Wolfram syndrome 1 (wolframin) 1 2
MIRT000166 TM9SF3 transmembrane 9 superfamily member 3 2 2
MIRT000167 RTN4 reticulon 4 2 2
MIRT000168 RPS7 ribosomal protein S7 5 17
MIRT000169 PLOD3 procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 2 2
MIRT000170 PDHA2 pyruvate dehydrogenase (lipoamide) alpha 2 1 2
MIRT000171 NCAPG non-SMC condensin I complex, subunit G 2 2
MIRT000172 DERL1 Der1-like domain family, member 1 3 3
MIRT000173 BASP1 brain abundant, membrane attached signal protein 1 2 3
MIRT000174 SPRY1 sprouty homolog 1, antagonist of FGF signaling (Drosophila) 1 1
MIRT000175 WNT1 wingless-type MMTV integration site family, member 1 1 1
MIRT000176 JAG1 jagged 1 (Alagille syndrome) 4 3
MIRT000177 REST RE1-silencing transcription factor 2 1
MIRT000672 SPRY2 sprouty homolog 2 (Drosophila) 3 4
MIRT000954 TIMP3 TIMP metallopeptidase inhibitor 3 5 4
MIRT000960 SOX5 SRY (sex determining region Y)-box 5 5 2
MIRT000961 MTAP methylthioadenosine phosphorylase 4 2
MIRT000969 RECK reversion-inducing-cysteine-rich protein with kazal motifs 5 7
MIRT001121 E2F2 E2F transcription factor 2 1 1
MIRT001188 FMOD fibromodulin 2 1
MIRT001189 TGFBR2 transforming growth factor, beta receptor II (70/80kDa) 5 5
MIRT001190 PTEN phosphatase and tensin homolog 5 33
MIRT001191 E2F1 E2F transcription factor 1 4 2
MIRT001208 TGFBI transforming growth factor, beta-induced, 68kDa 3 2
MIRT001220 LRRFIP1 leucine rich repeat (in FLII) interacting protein 1 4 3
MIRT001221 MARCKS myristoylated alanine-rich protein kinase C substrate 3 1
MIRT001980 TPM1 tropomyosin 1 (alpha) 5 9
MIRT002090 NFIB nuclear factor I/B 4 6
MIRT002406 CDK6 cyclin-dependent kinase 6 2 2
MIRT002407 RP2 retinitis pigmentosa 2 (X-linked recessive) 2 2
MIRT002408 SGK3 serum/glucocorticoid regulated kinase family, member 3 2 2
MIRT002409 SLC16A10 solute carrier family 16, member 10 (aromatic amino acid transporter) 2 2
MIRT002410 APAF1 apoptotic peptidase activating factor 1 5 3
MIRT002411 GLCCI1 glucocorticoid induced transcript 1 2 2
MIRT002412 SOCS5 suppressor of cytokine signaling 5 2 2
MIRT002414 SESN1 sestrin 1 2 2
MIRT002416 BTG2 BTG family, member 2 6 4
MIRT002418 PRRG4 proline rich Gla (G-carboxyglutamic acid) 4 (transmembrane) 1 1
MIRT002419 HIPK3 homeodomain interacting protein kinase 3 1 1
MIRT002420 FAM3C family with sequence similarity 3, member C 2 2
MIRT002421 FAS Fas (TNF receptor superfamily, member 6) 2 2
MIRT002422 CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1) 1 1
MIRT003054 PDCD4 programmed cell death 4 (neoplastic transformation inhibitor) 6 35
MIRT003146 Pdcd4 programmed cell death 4 3 1
MIRT003147 Pten phosphatase and tensin homolog 3 1
MIRT003317 RHOB ras homolog gene family, member B 4 4
MIRT003567 SERPINB5 serpin peptidase inhibitor, clade B (ovalbumin), member 5 4 7
MIRT003837 BMPR2 bone morphogenetic protein receptor, type II (serine/threonine kinase) 5 5
MIRT003988 RASA1 RAS p21 protein activator (GTPase activating protein) 1 3 1
MIRT004287 TGIF1 TGFB-induced factor homeobox 1 2 1
MIRT004306 NCOA3 nuclear receptor coactivator 3 2 1
MIRT004307 MYC v-myc myelocytomatosis viral oncogene homolog (avian) 2 1
MIRT004318 ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) 2 1
MIRT004812 SPATS2L spermatogenesis associated, serine-rich 2-like 1 1
MIRT004813 EIF2S1 eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa 1 1
MIRT004814 PCBP1 poly(rC) binding protein 1 2 2
MIRT004838 Pten phosphatase and tensin homolog 3 1
MIRT004839 Reck reversion-inducing-cysteine-rich protein with kazal motifs 3 1
MIRT005323 JMY junction mediating and regulatory protein, p53 cofactor 3 1
MIRT005324 TOPORS topoisomerase I binding, arginine/serine-rich 4 3
MIRT005325 HNRNPK heterogeneous nuclear ribonucleoprotein K 3 4
MIRT005327 DAXX death-domain associated protein 4 1
MIRT005328 TP53BP2 tumor protein p53 binding protein, 2 3 1
MIRT005329 TP63 tumor protein p63 4 2
MIRT005330 TGFBR3 transforming growth factor, beta receptor III 4 3
MIRT005331 PPIF peptidylprolyl isomerase F 3 2
MIRT005429 MSH2 mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) 5 3
MIRT005430 MSH6 mutS homolog 6 (E. coli) 4 1
MIRT005565 TIAM1 T-cell lymphoma invasion and metastasis 1 4 2
MIRT005717 ISCU iron-sulfur cluster scaffold homolog (E. coli) 3 1
MIRT005737 MEF2C myocyte enhancer factor 2C 1 1
MIRT005772 EIF4A2 eukaryotic translation initiation factor 4A2 4 1
MIRT005773 ANKRD46 ankyrin repeat domain 46 4 1
MIRT005807 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 4 2
MIRT005951 IL1B interleukin 1, beta 3 1
MIRT005952 ICAM1 intercellular adhesion molecule 1 3 1
MIRT005953 PLAT plasminogen activator, tissue 3 1
MIRT005954 PTX3 pentraxin 3, long 1 1
MIRT005955 TNFAIP3 tumor necrosis factor, alpha-induced protein 3 1 1
MIRT005956 CCR1 chemokine (C-C motif) receptor 1 1 1
MIRT005974 CDK2AP1 cyclin-dependent kinase 2 associated protein 1 3 2
MIRT006199 CCL20 chemokine (C-C motif) ligand 20 1 1
MIRT006236 SP1 Sp1 transcription factor 2 1
MIRT006288 PIAS3 protein inhibitor of activated STAT, 3 1 1
MIRT006313 DOCK4 dedicator of cytokinesis 4 2 1
MIRT006314 DOCK5 dedicator of cytokinesis 5 2 1
MIRT006315 DOCK7 dedicator of cytokinesis 7 2 1
MIRT006323 DUSP10 dual specificity phosphatase 10 3 1
MIRT006422 PPARA peroxisome proliferator-activated receptor alpha 4 2
MIRT006515 ANP32A acidic (leucine-rich) nuclear phosphoprotein 32 family, member A 3 1
MIRT006516 SMARCA4 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 3 1
MIRT006529 NFKB1 nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 1 1
MIRT006797 NTF3 neurotrophin 3 2 1
MIRT006821 COL4A1 collagen, type IV, alpha 1 2 1
MIRT006989 FASLG Fas ligand (TNF superfamily, member 6) 4 3
MIRT006997 SOD3 superoxide dismutase 3, extracellular 1 1
MIRT007085 TCF21 transcription factor 21 1 1
MIRT007362 SMAD7 SMAD family member 7 2 1
MIRT030661 PHIP pleckstrin homology domain interacting protein 1 1
MIRT030662 PALLD palladin, cytoskeletal associated protein 1 1
MIRT030663 BOC Boc homolog (mouse) 1 1
MIRT030664 DAAM1 dishevelled associated activator of morphogenesis 1 1 1
MIRT030665 C20orf194 chromosome 20 open reading frame 194 1 1
MIRT030666 COL5A2 collagen, type V, alpha 2 1 1
MIRT030667 TPRG1L tumor protein p63 regulated 1-like 1 1
MIRT030668 NIN ninein (GSK3B interacting protein) 1 1
MIRT030669 PPAP2A phosphatidic acid phosphatase type 2A 1 1
MIRT030670 TRIM38 tripartite motif-containing 38 1 1
MIRT030671 DDR2 discoidin domain receptor tyrosine kinase 2 1 1
MIRT030672 VPS54 vacuolar protein sorting 54 homolog (S. cerevisiae) 1 1
MIRT030673 KIAA1715 KIAA1715 1 1
MIRT030674 BAZ1B bromodomain adjacent to zinc finger domain, 1B 1 1
MIRT030675 LIN7C lin-7 homolog C (C. elegans) 1 1
MIRT030676 USP34 ubiquitin specific peptidase 34 1 1
MIRT030677 GNE glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase 1 1
MIRT030678 ZBTB8A zinc finger and BTB domain containing 8A 1 1
MIRT030679 CLOCK clock homolog (mouse) 1 1
MIRT030680 LPGAT1 lysophosphatidylglycerol acyltransferase 1 1 1
MIRT030681 NIPBL Nipped-B homolog (Drosophila) 1 1
MIRT030682 DDHD2 DDHD domain containing 2 1 1
MIRT030683 C2orf43 chromosome 2 open reading frame 43 1 1
MIRT030684 SGCB sarcoglycan, beta (43kDa dystrophin-associated glycoprotein) 1 1
MIRT030685 FANCI Fanconi anemia, complementation group I 1 1
MIRT030686 EDIL3 EGF-like repeats and discoidin I-like domains 3 1 1
MIRT030687 DTX3L deltex 3-like (Drosophila) 1 1
MIRT030688 IREB2 iron-responsive element binding protein 2 1 1
MIRT030689 MGAT4A mannosyl (alpha-1,3-)-glycoprotein beta-1,4-N-acetylglucosaminyltransferase, isozyme A 1 1
MIRT030690 RAPH1 Ras association (RalGDS/AF-6) and pleckstrin homology domains 1 1 1
MIRT030691 CYBRD1 cytochrome b reductase 1 1 1
MIRT030692 SLAIN2 SLAIN motif family, member 2 1 1
MIRT030693 KIAA1551 chromosome 12 open reading frame 35 1 1
MIRT030694 SOX2 SRY (sex determining region Y)-box 2 1 1
MIRT030695 GTF2A1 general transcription factor IIA, 1, 19/37kDa 1 1
MIRT030696 RRAGC Ras-related GTP binding C 1 1
MIRT030697 PIGN phosphatidylinositol glycan anchor biosynthesis, class N 1 1
MIRT030698 HPS5 Hermansky-Pudlak syndrome 5 1 1
MIRT030699 SESTD1 SEC14 and spectrin domains 1 1 1
MIRT030700 MEF2A myocyte enhancer factor 2A 1 1
MIRT030701 ZBTB47 zinc finger and BTB domain containing 47 1 1
MIRT030702 ELOVL4 elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 4 1 1
MIRT030703 EPHA4 EPH receptor A4 1 1
MIRT030704 ENAH enabled homolog (Drosophila) 1 1
MIRT030705 TBL1XR1 transducin (beta)-like 1 X-linked receptor 1 1 1
MIRT030706 NBEA neurobeachin 1 1
MIRT030707 TAF5 TAF5 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 100kDa 1 1
MIRT030708 AP3M1 adaptor-related protein complex 3, mu 1 subunit 1 1
MIRT030709 CD47 CD47 molecule 1 1
MIRT030710 LATS1 LATS, large tumor suppressor, homolog 1 (Drosophila) 1 1
MIRT030711 CPEB3 cytoplasmic polyadenylation element binding protein 3 1 1
MIRT030712 RMND5A required for meiotic nuclear division 5 homolog A (S. cerevisiae) 1 1
MIRT030713 KBTBD7 kelch repeat and BTB (POZ) domain containing 7 1 1
MIRT030714 MEIS1 Meis homeobox 1 1 1
MIRT030715 GNB4 guanine nucleotide binding protein (G protein), beta polypeptide 4 1 1
MIRT030716 MMP2 matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase) 1 1
MIRT030717 VEGFA vascular endothelial growth factor A 2 2
MIRT030718 REV3L REV3-like, catalytic subunit of DNA polymerase zeta (yeast) 1 1
MIRT030719 TXLNG2P chromosome Y open reading frame 15A 1 1
MIRT030720 KLHL3 kelch-like 3 (Drosophila) 1 1
MIRT030721 SCAF11 splicing factor, arginine/serine-rich 2, interacting protein 1 1
MIRT030722 ACAP2 ArfGAP with coiled-coil, ankyrin repeat and PH domains 2 1 1
MIRT030723 HNRNPH1 heterogeneous nuclear ribonucleoprotein H1 (H) 1 1
MIRT030724 PARP1 poly (ADP-ribose) polymerase 1 1 1
MIRT030725 CERS6 LAG1 homolog, ceramide synthase 6 1 1
MIRT030726 SNX13 sorting nexin 13 1 1
MIRT030727 SNRNP48 small nuclear ribonucleoprotein 48kDa (U11/U12) 1 1
MIRT030728 FUBP1 far upstream element (FUSE) binding protein 1 1 1
MIRT030729 RTF1 Rtf1, Paf1/RNA polymerase II complex component, homolog (S. cerevisiae) 1 1
MIRT030730 TGFB1 transforming growth factor, beta 1 1 1
MIRT030731 ANKRD28 ankyrin repeat domain 28 1 1
MIRT030732 SYNE2 spectrin repeat containing, nuclear envelope 2 1 1
MIRT030733 OSBPL1A oxysterol binding protein-like 1A 1 1
MIRT030734 RSPRY1 ring finger and SPRY domain containing 1 1 1
MIRT030735 SRSF11 splicing factor, arginine/serine-rich 11 1 1
MIRT030736 ASRGL1 asparaginase like 1 1 1
MIRT030737 CUL3 cullin 3 1 1
MIRT030738 RB1 retinoblastoma 1 1 1
MIRT030739 TSN translin 1 1
MIRT030740 EXOC8 exocyst complex component 8 1 1
MIRT030741 IVNS1ABP influenza virus NS1A binding protein 1 1
MIRT030742 UTRN utrophin 1 1
MIRT030743 RASSF9 Ras association (RalGDS/AF-6) domain family (N-terminal) member 9 1 1
MIRT030744 ACAT1 acetyl-CoA acetyltransferase 1 1 1
MIRT030745 PFKFB2 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 1 1
MIRT030746 PDGFD platelet derived growth factor D 1 1
MIRT030747 COBLL1 COBL-like 1 1 1
MIRT030748 SAMD5 sterile alpha motif domain containing 5 1 1
MIRT030749 MOAP1 modulator of apoptosis 1 1 1
MIRT030750 KLHL24 kelch-like 24 (Drosophila) 1 1
MIRT030751 ZNF326 zinc finger protein 326 1 1
MIRT030752 WHSC1 Wolf-Hirschhorn syndrome candidate 1 1 1
MIRT030753 BTBD7 BTB (POZ) domain containing 7 1 1
MIRT030754 GAPVD1 GTPase activating protein and VPS9 domains 1 1 1
MIRT030755 TNS3 tensin 3 1 1
MIRT030756 ESYT2 extended synaptotagmin-like protein 2 1 1
MIRT030757 MYEF2 myelin expression factor 2 1 1
MIRT030758 PPP1R3B protein phosphatase 1, regulatory (inhibitor) subunit 3B 1 1
MIRT030759 PKD2 polycystic kidney disease 2 (autosomal dominant) 1 1
MIRT030760 PTAR1 protein prenyltransferase alpha subunit repeat containing 1 1 1
MIRT030761 PAN3 PAN3 poly(A) specific ribonuclease subunit homolog (S. cerevisiae) 1 1
MIRT030762 ZRANB1 zinc finger, RAN-binding domain containing 1 1 1
MIRT030763 MON2 MON2 homolog (S. cerevisiae) 1 1
MIRT030764 RASEF RAS and EF-hand domain containing 1 1
MIRT030765 GNAQ guanine nucleotide binding protein (G protein), q polypeptide 1 1
MIRT030766 HERPUD2 HERPUD family member 2 1 1
MIRT030767 MAP3K2 mitogen-activated protein kinase kinase kinase 2 1 1
MIRT030768 THOC2 THO complex 2 1 1
MIRT030769 RASGRP3 RAS guanyl releasing protein 3 (calcium and DAG-regulated) 1 1
MIRT030770 PHF17 PHD finger protein 17 1 1
MIRT030771 USP7 ubiquitin specific peptidase 7 (herpes virus-associated) 1 1
MIRT030772 GTF2I general transcription factor IIi 1 1
MIRT030773 MKNK2 MAP kinase interacting serine/threonine kinase 2 1 1
MIRT030774 CLCN5 chloride channel 5 1 1
MIRT030775 TRIM2 tripartite motif-containing 2 1 1
MIRT030776 LONRF2 LON peptidase N-terminal domain and ring finger 2 1 1
MIRT030777 EIF4EBP2 eukaryotic translation initiation factor 4E binding protein 2 1 1
MIRT030778 PHF16 PHD finger protein 16 1 1
MIRT030779 ELOVL7 ELOVL family member 7, elongation of long chain fatty acids (yeast) 1 1
MIRT030780 VPS41 vacuolar protein sorting 41 homolog (S. cerevisiae) 1 1
MIRT030781 SASH1 SAM and SH3 domain containing 1 1 1
MIRT030782 RAB22A RAB22A, member RAS oncogene family 1 1
MIRT030783 SUZ12 suppressor of zeste 12 homolog (Drosophila) 1 1
MIRT030784 SPIN1 spindlin 1 1 1
MIRT030785 POLR3B polymerase (RNA) III (DNA directed) polypeptide B 1 1
MIRT030786 ATP2B4 ATPase, Ca++ transporting, plasma membrane 4 1 1
MIRT030787 CCDC34 coiled-coil domain containing 34 1 1
MIRT030788 PGRMC2 progesterone receptor membrane component 2 1 1
MIRT030789 TRPM7 transient receptor potential cation channel, subfamily M, member 7 1 1
MIRT030790 GID4 chromosome 17 open reading frame 39 1 1
MIRT030791 FAM63B family with sequence similarity 63, member B 1 1
MIRT030792 PLEKHA1 pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 1 1 1
MIRT030793 MALT1 mucosa associated lymphoid tissue lymphoma translocation gene 1 1 1
MIRT030794 ZNF367 zinc finger protein 367 1 1
MIRT030795 TMEM245 chromosome 9 open reading frame 5 1 1
MIRT030796 MBNL1 muscleblind-like (Drosophila) 1 1
MIRT030797 MORC3 MORC family CW-type zinc finger 3 1 1
MIRT030798 ZNF35 zinc finger protein 35 1 1
MIRT030799 PSRC1 proline/serine-rich coiled-coil 1 1 1
MIRT030800 FOXN3 forkhead box N3 1 1
MIRT030801 NR2C2 nuclear receptor subfamily 2, group C, member 2 1 1
MIRT030802 FBXO3 F-box protein 3 1 1
MIRT030803 GPAM glycerol-3-phosphate acyltransferase, mitochondrial 1 1
MIRT030804 PM20D2 peptidase M20 domain containing 2 1 1
MIRT030805 CLIP4 CAP-GLY domain containing linker protein family, member 4 1 1
MIRT030806 DMTF1 cyclin D binding myb-like transcription factor 1 1 1
MIRT030807 DDX46 DEAD (Asp-Glu-Ala-Asp) box polypeptide 46 1 1
MIRT030808 ATRX alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae) 1 1
MIRT030809 LMBR1 limb region 1 homolog (mouse) 1 1
MIRT030810 MUC1 mucin 1, cell surface associated 1 1
MIRT030811 IL6R interleukin 6 receptor 1 1
MIRT030812 TUBGCP5 tubulin, gamma complex associated protein 5 1 1
MIRT030813 RHOQ ras homolog gene family, member Q 1 1
MIRT030814 TET1 tet oncogene 1 1 1
MIRT030815 CASC5 cancer susceptibility candidate 5 1 1
MIRT030816 ARHGAP21 Rho GTPase activating protein 21 1 1
MIRT030817 MDM4 Mdm4 p53 binding protein homolog (mouse) 1 1
MIRT030818 LARS leucyl-tRNA synthetase 1 1
MIRT030819 FAXDC2 chromosome 5 open reading frame 4 1 1
MIRT030820 CDK19 cyclin-dependent kinase 19 1 1
MIRT030821 LAMP2 lysosomal-associated membrane protein 2 1 1
MIRT030822 MOXD1 monooxygenase, DBH-like 1 1 1
MIRT030823 AHSA2 AHA1, activator of heat shock 90kDa protein ATPase homolog 2 (yeast) 1 1
MIRT030824 PIK3C2A phosphoinositide-3-kinase, class 2, alpha polypeptide 1 1
MIRT030825 TMEM2 transmembrane protein 2 1 1
MIRT030826 IPP intracisternal A particle-promoted polypeptide 1 1
MIRT030827 RAI14 retinoic acid induced 14 1 1
MIRT030828 MYO9A myosin IXA 1 1
MIRT030829 MRPS10 mitochondrial ribosomal protein S10 1 1
MIRT030830 FBXL17 F-box and leucine-rich repeat protein 17 1 1
MIRT030831 AGGF1 angiogenic factor with G patch and FHA domains 1 1 1
MIRT030832 SLC26A2 solute carrier family 26 (sulfate transporter), member 2 1 1
MIRT030833 PRKAB2 protein kinase, AMP-activated, beta 2 non-catalytic subunit 1 1
MIRT030834 SREK1 splicing factor, arginine/serine-rich 12 1 1
MIRT030835 FAM20B family with sequence similarity 20, member B 1 1
MIRT030836 ARMCX3 armadillo repeat containing, X-linked 3 1 1
MIRT030837 SERPINI1 serpin peptidase inhibitor, clade I (neuroserpin), member 1 1 1
MIRT030838 DDAH1 dimethylarginine dimethylaminohydrolase 1 1 1
MIRT030839 PROSER1 chromosome 13 open reading frame 23 1 1
MIRT030840 PRICKLE2 prickle homolog 2 (Drosophila) 1 1
MIRT030841 JPH1 junctophilin 1 1 1
MIRT030842 NAA30 N(alpha)-acetyltransferase 30, NatC catalytic subunit 1 1
MIRT030843 FKBP5 FK506 binding protein 5 1 1
MIRT030844 TGFB2 transforming growth factor, beta 2 1 1
MIRT030845 ZMYM2 zinc finger, MYM-type 2 1 1
MIRT030846 TRIM33 tripartite motif-containing 33 1 1
MIRT030847 RAPGEF6 Rap guanine nucleotide exchange factor (GEF) 6 1 1
MIRT030848 MTPN myotrophin 1 1
MIRT030849 GOLGA4 golgin A4 1 1
MIRT030850 SACM1L SAC1 suppressor of actin mutations 1-like (yeast) 1 1
MIRT030851 ATAD2B ATPase family, AAA domain containing 2B 1 1
MIRT030852 FIGN fidgetin 1 1
MIRT030853 EPM2A epilepsy, progressive myoclonus type 2A, Lafora disease (laforin) 1 1
MIRT030854 RAB6C RAB6C, member RAS oncogene family 1 1
MIRT030855 TSNAX translin-associated factor X 1 1
MIRT030856 TRAPPC2 trafficking protein particle complex 2 1 1
MIRT030857 LIFR leukemia inhibitory factor receptor alpha 1 1
MIRT030858 CALD1 caldesmon 1 1 1
MIRT030859 LYRM7 Lyrm7 homolog (mouse) 1 1
MIRT030860 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 1 1
MIRT030861 RPS6KA3 ribosomal protein S6 kinase, 90kDa, polypeptide 3 1 1
MIRT030862 ADNP activity-dependent neuroprotector homeobox 1 1
MIRT030863 LRRC57 leucine rich repeat containing 57 1 1
MIRT030864 DUSP8 dual specificity phosphatase 8 1 1
MIRT030865 KLHL15 kelch-like 15 (Drosophila) 1 1
MIRT030866 GXYLT2 glucoside xylosyltransferase 2 1 1
MIRT030867 PBRM1 polybromo 1 1 1
MIRT030868 SMNDC1 survival motor neuron domain containing 1 1 1
MIRT030869 NCSTN nicastrin 1 1
MIRT030870 PPM1L protein phosphatase, Mg2+/Mn2+ dependent, 1L 1 1
MIRT030871 MMP9 matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) 1 1
MIRT030872 PARP9 poly (ADP-ribose) polymerase family, member 9 1 1
MIRT030873 CKAP5 cytoskeleton associated protein 5 1 1
MIRT030874 CAPRIN1 cell cycle associated protein 1 1 1
MIRT030875 CNTRL centrosomal protein 110kDa 1 1
MIRT030876 PHTF1 putative homeodomain transcription factor 1 1 1
MIRT030877 MRAP2 melanocortin 2 receptor accessory protein 2 1 1
MIRT030878 MYCBP2 MYC binding protein 2 1 1
MIRT030879 ITSN2 intersectin 2 1 1
MIRT030880 BCAT1 branched chain amino-acid transaminase 1, cytosolic 1 1
MIRT030881 PPFIA4 protein tyrosine phosphatase, receptor type, f polypeptide (PTPRF), interacting protein (liprin), alpha 4 1 1
MIRT030882 YME1L1 YME1-like 1 (S. cerevisiae) 1 1
MIRT030883 ZNF667 zinc finger protein 667 1 1
MIRT030884 ETNK1 ethanolamine kinase 1 1 1
MIRT030885 CYP4V2 cytochrome P450, family 4, subfamily V, polypeptide 2 1 1
MIRT030886 BRCA1 breast cancer 1, early onset 1 1
MIRT030887 DOCK10 dedicator of cytokinesis 10 1 1
MIRT030888 DMD dystrophin 1 1
MIRT030889 TMX4 thioredoxin-related transmembrane protein 4 1 1
MIRT030890 PTBP3 ROD1 regulator of differentiation 1 (S. pombe) 1 1
MIRT030891 APOLD1 apolipoprotein L domain containing 1 1 1
MIRT030892 CCT6P1 chaperonin containing TCP1, subunit 6 (zeta) pseudogene 1 1 1
MIRT030893 UBR3 ubiquitin protein ligase E3 component n-recognin 3 (putative) 1 1
MIRT030894 NEK1 NIMA (never in mitosis gene a)-related kinase 1 1 1
MIRT030895 DYNC1LI2 dynein, cytoplasmic 1, light intermediate chain 2 1 1
MIRT030896 CSNK1A1 casein kinase 1, alpha 1 1 1
MIRT030897 ACTR2 ARP2 actin-related protein 2 homolog (yeast) 1 1
MIRT030898 TRIM59 tripartite motif-containing 59 1 1
MIRT030899 SPTLC3 serine palmitoyltransferase, long chain base subunit 3 1 1
MIRT030900 TMEM56 transmembrane protein 56 1 1
MIRT030901 ZADH2 zinc binding alcohol dehydrogenase domain containing 2 1 1
MIRT030902 DDX3X DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked 1 1
MIRT030903 ZNF217 zinc finger protein 217 1 1
MIRT030904 FAM217B chromosome 20 open reading frame 177 1 1
MIRT030905 ZBTB20 zinc finger and BTB domain containing 20 1 1
MIRT030906 FNBP1 formin binding protein 1 1 1
MIRT030907 ZFYVE16 zinc finger, FYVE domain containing 16 1 1
MIRT030908 VPS13A vacuolar protein sorting 13 homolog A (S. cerevisiae) 1 1
MIRT030909 B3GALNT1 beta-1,3-N-acetylgalactosaminyltransferase 1 (globoside blood group) 1 1
MIRT030910 SLC5A3 solute carrier family 5 (sodium/myo-inositol cotransporter), member 3 1 1
MIRT030911 GPD1L glycerol-3-phosphate dehydrogenase 1-like 1 1
MIRT030912 STRBP spermatid perinuclear RNA binding protein 1 1
MIRT030913 PRKCE protein kinase C, epsilon 1 1
MIRT030914 TOP2A topoisomerase (DNA) II alpha 170kDa 1 1
MIRT030915 SEC63 SEC63 homolog (S. cerevisiae) 1 1
MIRT030916 TAF1 TAF1 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 250kDa 1 1
MIRT030917 MPP5 membrane protein, palmitoylated 5 (MAGUK p55 subfamily member 5) 1 1
MIRT030918 PTK2 PTK2 protein tyrosine kinase 2 1 1
MIRT030919 GPD2 glycerol-3-phosphate dehydrogenase 2 (mitochondrial) 1 1
MIRT030920 SSFA2 sperm specific antigen 2 1 1
MIRT030921 HECTD1 HECT domain containing 1 1 1
MIRT030922 PAG1 phosphoprotein associated with glycosphingolipid microdomains 1 1 1
MIRT030923 SFXN1 sideroflexin 1 1 1
MIRT030924 HAPLN1 hyaluronan and proteoglycan link protein 1 1 1
MIRT030925 EIF5 eukaryotic translation initiation factor 5 1 1
MIRT030926 KLHL42 kelch domain containing 5 1 1
MIRT030927 NFAT5 nuclear factor of activated T-cells 5, tonicity-responsive 1 1
MIRT030928 SLC9A6 solute carrier family 9 (sodium/hydrogen exchanger), member 6 1 1
MIRT030929 ZNF207 zinc finger protein 207 1 1
MIRT030930 RALGPS2 Ral GEF with PH domain and SH3 binding motif 2 1 1
MIRT030931 FAM46A family with sequence similarity 46, member A 1 1
MIRT030932 MTMR12 myotubularin related protein 12 1 1
MIRT030933 KBTBD6 kelch repeat and BTB (POZ) domain containing 6 1 1
MIRT030934 TNRC6B trinucleotide repeat containing 6B 1 1
MIRT030935 ABCD3 ATP-binding cassette, sub-family D (ALD), member 3 1 1
MIRT030936 PKNOX1 PBX/knotted 1 homeobox 1 1 1
MIRT030937 RAB11FIP2 RAB11 family interacting protein 2 (class I) 1 1
MIRT030938 PURB purine-rich element binding protein B 1 1
MIRT030939 LCORL ligand dependent nuclear receptor corepressor-like 1 1
MIRT030940 KLF5 Kruppel-like factor 5 (intestinal) 1 1
MIRT030941 ST6GAL1 ST6 beta-galactosamide alpha-2,6-sialyltranferase 1 1 1
MIRT030942 GPR64 G protein-coupled receptor 64 1 1
MIRT030943 SKP2 S-phase kinase-associated protein 2 (p45) 1 1
MIRT030944 ECI2 peroxisomal D3,D2-enoyl-CoA isomerase 1 1
MIRT030945 NUFIP2 nuclear fragile X mental retardation protein interacting protein 2 1 1
MIRT030946 GRPEL2 GrpE-like 2, mitochondrial (E. coli) 1 1
MIRT030947 HS3ST3B1 heparan sulfate (glucosamine) 3-O-sulfotransferase 3B1 1 1
MIRT030948 ELAVL4 ELAV (embryonic lethal, abnormal vision, Drosophila)-like 4 (Hu antigen D) 1 1
MIRT030949 CORO2A coronin, actin binding protein, 2A 1 1
MIRT030950 TTC33 tetratricopeptide repeat domain 33 1 2
MIRT030951 AUTS2 autism susceptibility candidate 2 2 2
MIRT030952 AKAP9 A kinase (PRKA) anchor protein (yotiao) 9 1 1
MIRT030953 NKTR natural killer-tumor recognition sequence 1 2
MIRT030954 PTPN14 protein tyrosine phosphatase, non-receptor type 14 1 1
MIRT030955 STXBP5 syntaxin binding protein 5 (tomosyn) 1 1
MIRT030956 MGA MAX gene associated 1 3
MIRT030957 SMC5 structural maintenance of chromosomes 5 1 1
MIRT030958 KIFAP3 kinesin-associated protein 3 1 1
MIRT030959 SPG11 spastic paraplegia 11 (autosomal recessive) 1 1
MIRT030960 PER3 period homolog 3 (Drosophila) 1 1
MIRT030961 ZNF292 zinc finger protein 292 1 1
MIRT030962 ZNF587 zinc finger protein 587 1 1
MIRT030963 AIM1 absent in melanoma 1 1 1
MIRT030964 DSE dermatan sulfate epimerase 1 1
MIRT030965 SRPK2 SFRS protein kinase 2 1 1
MIRT030966 TSHZ3 teashirt zinc finger homeobox 3 1 1
MIRT030967 CEP97 centrosomal protein 97kDa 1 1
MIRT030968 DCAF10 DDB1 and CUL4 associated factor 10 1 1
MIRT030969 PHF20 PHD finger protein 20 1 1
MIRT030970 SEMA5A sema domain, seven thrombospondin repeats (type 1 and type 1-like), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 5A 1 1
MIRT030971 PHACTR2 phosphatase and actin regulator 2 1 1
MIRT030972 RABGAP1 RAB GTPase activating protein 1 1 1
MIRT030973 VPS36 vacuolar protein sorting 36 homolog (S. cerevisiae) 1 1
MIRT030974 WNK1 WNK lysine deficient protein kinase 1 1 1
MIRT030975 NUBPL nucleotide binding protein-like 1 1
MIRT030976 LIMCH1 LIM and calponin homology domains 1 1 1
MIRT030977 MTMR9 myotubularin related protein 9 1 1
MIRT030978 SERAC1 serine active site containing 1 1 1
MIRT030979 RUFY3 RUN and FYVE domain containing 3 1 1
MIRT030980 APPL1 adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 1 1 1
MIRT030981 PBX1 pre-B-cell leukemia homeobox 1 1 1
MIRT030982 OSBPL3 oxysterol binding protein-like 3 1 1
MIRT030983 WNT5A wingless-type MMTV integration site family, member 5A 1 1
MIRT030984 REV1 REV1 homolog (S. cerevisiae) 1 1
MIRT030985 FBXL2 F-box and leucine-rich repeat protein 2 1 1
MIRT030986 HOXA9 homeobox A9 1 1
MIRT030987 MIB1 mindbomb homolog 1 (Drosophila) 1 1
MIRT030988 FMR1 fragile X mental retardation 1 1 1
MIRT030989 SNX30 sorting nexin family member 30 1 1
MIRT030990 SLC17A5 solute carrier family 17 (anion/sugar transporter), member 5 1 1
MIRT030991 PREPL prolyl endopeptidase-like 1 1
MIRT030992 CCDC14 coiled-coil domain containing 14 1 1
MIRT030993 ARHGEF12 Rho guanine nucleotide exchange factor (GEF) 12 1 1
MIRT030994 USP47 ubiquitin specific peptidase 47 1 1
MIRT030995 BTBD3 BTB (POZ) domain containing 3 1 1
MIRT030996 ARID4A AT rich interactive domain 4A (RBP1-like) 1 1
MIRT030997 ATP11B ATPase, class VI, type 11B 1 1
MIRT030998 SLC31A1 solute carrier family 31 (copper transporters), member 1 1 1
MIRT030999 DLG1 discs, large homolog 1 (Drosophila) 1 1
MIRT031000 SOWAHC ankyrin repeat domain 57 1 1
MIRT031001 RSF1 remodeling and spacing factor 1 1 1
MIRT031002 SNRK SNF related kinase 1 1
MIRT031003 PLD1 phospholipase D1, phosphatidylcholine-specific 1 1
MIRT031004 TLR4 toll-like receptor 4 1 1
MIRT031005 VPS26A vacuolar protein sorting 26 homolog A (S. pombe) 1 1
MIRT031006 ZYG11B zyg-11 homolog B (C. elegans) 1 1
MIRT031007 AGO4 eukaryotic translation initiation factor 2C, 4 1 1
MIRT031008 TESK2 testis-specific kinase 2 1 1
MIRT031009 MAP3K1 mitogen-activated protein kinase kinase kinase 1 1 1
MIRT031010 RAB6A RAB6A, member RAS oncogene family 1 1
MIRT031011 PURA purine-rich element binding protein A 1 1
MIRT031012 OLR1 oxidized low density lipoprotein (lectin-like) receptor 1 1 1
MIRT031013 KLF9 Kruppel-like factor 9 1 1
MIRT031014 ATMIN ATM interactor 1 1
MIRT031015 PRPF39 PRP39 pre-mRNA processing factor 39 homolog (S. cerevisiae) 1 1
MIRT031016 AGO2 eukaryotic translation initiation factor 2C, 2 1 1
MIRT031017 STAG2 stromal antigen 2 1 1
MIRT031018 ACBD5 acyl-CoA binding domain containing 5 2 2
MIRT031019 AKT2 v-akt murine thymoma viral oncogene homolog 2 2 1
MIRT031020 UGGT1 UDP-glucose glycoprotein glucosyltransferase 1 1 1
MIRT031021 PRRC1 proline-rich coiled-coil 1 1 1
MIRT031022 NT5C2 5'-nucleotidase, cytosolic II 1 1
MIRT031023 ZNF532 zinc finger protein 532 1 1
MIRT031024 DCAF8 DDB1 and CUL4 associated factor 8 1 1
MIRT031025 TCF4 transcription factor 4 1 1
MIRT031026 UBR5 ubiquitin protein ligase E3 component n-recognin 5 1 1
MIRT031027 THBS1 thrombospondin 1 1 1
MIRT031028 PTPN3 protein tyrosine phosphatase, non-receptor type 3 1 1
MIRT031029 ATF2 activating transcription factor 2 1 1
MIRT031030 RBM27 RNA binding motif protein 27 1 1
MIRT031031 EXOC5 exocyst complex component 5 1 1
MIRT031032 AFTPH aftiphilin 1 1
MIRT031033 BID BH3 interacting domain death agonist 1 1
MIRT031034 KLHL8 kelch-like 8 (Drosophila) 1 1
MIRT031035 WDR7 WD repeat domain 7 1 1
MIRT031036 FAM126B family with sequence similarity 126, member B 1 1
MIRT031037 PTGFR prostaglandin F receptor (FP) 1 1
MIRT031038 PHF20L1 PHD finger protein 20-like 1 1 1
MIRT031039 B3GNT5 UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 5 1 1
MIRT031040 GLG1 golgi glycoprotein 1 1 1
MIRT031041 CEP152 centrosomal protein 152kDa 1 1
MIRT031042 HMGB3 high-mobility group box 3 1 1
MIRT031043 BDH2 3-hydroxybutyrate dehydrogenase, type 2 1 1
MIRT031044 LPIN1 lipin 1 1 1
MIRT031045 NETO2 neuropilin (NRP) and tolloid (TLL)-like 2 1 1
MIRT031046 BRMS1L breast cancer metastasis-suppressor 1-like 1 1
MIRT031047 NEK7 NIMA (never in mitosis gene a)-related kinase 7 1 1
MIRT031048 TSC1 tuberous sclerosis 1 1 1
MIRT031049 ALMS1 Alstrom syndrome 1 1 1
MIRT031050 TOR1AIP2 torsin A interacting protein 2 1 1
MIRT031051 SMC1A structural maintenance of chromosomes 1A 1 1
MIRT031052 PIGX phosphatidylinositol glycan anchor biosynthesis, class X 1 1
MIRT031053 SAR1A SAR1 homolog A (S. cerevisiae) 1 1
MIRT031054 APC adenomatous polyposis coli 1 1
MIRT031055 SLMAP sarcolemma associated protein 1 1
MIRT031056 SOCS4 suppressor of cytokine signaling 4 1 1
MIRT031057 ZBTB38 zinc finger and BTB domain containing 38 1 1
MIRT031058 OSR1 odd-skipped related 1 (Drosophila) 1 1
MIRT031059 FBXO11 F-box protein 11 1 1
MIRT031060 SCRN1 secernin 1 1 1
MIRT031061 PTPDC1 protein tyrosine phosphatase domain containing 1 1 1
MIRT031062 CCNG1 cyclin G1 1 1
MIRT031063 MEGF9 multiple EGF-like-domains 9 1 1
MIRT031064 TNPO1 transportin 1 1 1
MIRT031065 FERMT2 fermitin family homolog 2 (Drosophila) 1 1
MIRT031066 KAT6A MYST histone acetyltransferase (monocytic leukemia) 3 1 1
MIRT031067 TNFRSF11B tumor necrosis factor receptor superfamily, member 11b 1 1
MIRT031068 WWC2 WW and C2 domain containing 2 1 2
MIRT031069 WNK3 WNK lysine deficient protein kinase 3 1 1
MIRT031070 WHSC1L1 Wolf-Hirschhorn syndrome candidate 1-like 1 1 1
MIRT031071 VASH2 vasohibin 2 1 2
MIRT031072 SLK STE20-like kinase (yeast) 1 2
MIRT031073 FILIP1L filamin A interacting protein 1-like 1 2
MIRT031074 DCP1A DCP1 decapping enzyme homolog A (S. cerevisiae) 1 4
MIRT031075 RNF11 ring finger protein 11 1 2
MIRT031076 RDH11 retinol dehydrogenase 11 (all-trans/9-cis/11-cis) 1 4
MIRT031077 PELI1 pellino homolog 1 (Drosophila) 2 2
MIRT031078 YOD1 YOD1 OTU deubiquinating enzyme 1 homolog (S. cerevisiae) 2 2
MIRT031079 STAT3 signal transducer and activator of transcription 3 (acute-phase response factor) 3 2
MIRT035524 BCL6 B-cell CLL/lymphoma 6 1 1
MIRT050474 OTUD1 OTU domain containing 1 1 1
MIRT050475 TMEM147 transmembrane protein 147 1 1