Accession ID: MIRT001190 [miRNA, hsa-miR-21 ::
PTEN, target gene]
| pre-miRNA ID | hsa-mir-21 LinkOut: [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 |  |
| Mature miRNA | hsa-miR-21-3p |
|---|---|
| Mature Sequence | 46| CAACACCAGUCGAUGGGCUGU |66 |
| Evidence | Experimental |
| Experiments | Cloned |
| Putative hsa-miR-21-3p Targets | LinkOut: [ TargetScanS 5.1 | MicroCosm | microRNA.org | miRecords | miRDB | miRo | miRNAMap 2.0 ] |
| Mature miRNA | hsa-miR-21-5p |
| Mature Sequence | 8| UAGCUUAUCAGACUGAUGUUGA |29 |
| Evidence | Experimental |
| Experiments | Cloned |
| Putative hsa-miR-21-5p Targets | LinkOut: [ TargetScanS 5.1 | MicroCosm | microRNA.org | miRecords | miRDB | miRo | miRNAMap 2.0 ] |
 |
| 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_000314 LinkOut: [ RefSeq ] | ||||||||||||||||||||
| Expression | LinkOut: [ BioGPS ] | ||||||||||||||||||||
| KEGG Pathway |
hsa00562 Inositol phosphate metabolism - Homo sapiens (human) hsa04070 Phosphatidylinositol signaling system - Homo sapiens (human) hsa04115 p53 signaling pathway - Homo sapiens (human) hsa04510 Focal adhesion - Homo sapiens (human) hsa04530 Tight junction - Homo sapiens (human) hsa05200 Pathways in cancer - Homo sapiens (human) hsa05213 Endometrial cancer - Homo sapiens (human) hsa05214 Glioma - Homo sapiens (human) hsa05215 Prostate cancer - Homo sapiens (human) hsa05218 Melanoma - Homo sapiens (human) hsa05222 Small cell lung cancer - Homo sapiens (human) |
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| Putative miRNA Targets on PTEN | LinkOut: [ TargetScan 5.1 | MicroCosm | miRNAMap 2.0 ] | ||||||||||||||||||||
| 3'UTR of PTEN (miRNA target sites are highlighted) |
>PTEN|NM_000314|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 |
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| miRNA-target interactions (Predicted by miRanda) |
|
| miRNA:Target | hsa-miR-21 :: PTEN [ Functional MTI ] |
|---|---|
| Validation Method | Northern blot , qRT-PCR , Western blot |
| Conditions | KMCH-1, mz-ChA-1, TFK |
| 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]
|
| miRNA:Target | hsa-miR-21 :: PTEN [ Functional MTI ] |
|---|---|
| Validation Method | Immunocytochemistry , Luciferase reporter assay , Northern blot , qRT-PCR , Western blot , Microarray |
| Conditions | HCC, SK-HEP-1, SNU-182 |
| 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]
|
| miRNA:Target | hsa-miR-21 :: PTEN [ Functional MTI ] |
|---|---|
| Validation Method | Luciferase reporter assay , qRT-PCR , Western blot |
| Location of target site | 3'UTR, unknown |
| 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 |
An autoregulatory loop mediated by miR-21 and PDCD4 controls the AP-1 activity in RAS transformation
- 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]
|
| miRNA:Target | hsa-miR-21 :: PTEN [ Functional MTI ] |
|---|---|
| Validation Method | Luciferase reporter assay |
| 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]
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| miRNA:Target | hsa-miR-21 :: 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]
|
| miRNA:Target | hsa-miR-21 :: 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]
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| miRNA:Target | hsa-miR-21 :: 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]
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| miRNA:Target | hsa-miR-21 :: 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]
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| miRNA:Target | hsa-miR-21 :: PTEN [ Functional MTI ] |
|---|---|
| Validation Method | Western blot |
| 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]
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| miRNA:Target | hsa-miR-21 :: PTEN [ Functional MTI ] |
|---|---|
| Validation Method | qRT-PCR , Western blot |
| 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]
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| miRNA:Target | hsa-miR-21 :: PTEN [ Functional MTI ] |
|---|---|
| Validation Method | Luciferase reporter assay , Western blot |
| 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]
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| miRNA:Target | hsa-miR-21 :: 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]
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| miRNA:Target | hsa-miR-21 :: 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. |
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| miRNA-target interactions (Provided by authors) |
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| 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]
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| miRNA:Target | hsa-miR-21 :: 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]
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| miRNA:Target | hsa-miR-21 :: 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]
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| miRNA:Target | hsa-miR-21 :: PTEN [ Functional MTI ] |
|---|---|
| Validation Method | Immunohistochemistry , qRT-PCR , Western blot |
| Conditions | PLC/PRF/5, HuH7, HLE, HLF, Hep G2 |
| 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]
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| miRNA:Target | hsa-miR-21 :: 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]
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| miRNA:Target | hsa-miR-21 :: PTEN [ Functional MTI ] |
|---|---|
| Validation Method | Luciferase reporter assay , qRT-PCR , Western blot |
| Conditions | MCF-7 |
| 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]
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| miRNA:Target | hsa-miR-21 :: 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 |
| 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-21not 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]
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