Accession ID: MIRT002958 [miRNA, hsa-miR-19a-3p :: PTEN, target gene]
pre-miRNA Information
pre-miRNA ID hsa-mir-19aLinkOut: [miRBase ]
Synonyms MIRN19A, hsa-mir-19a, miR-19a, miRNA19A, MIR19A
Description Homo sapiens miR-19a stem-loop
Comment This sequence maps to chromosome 13 and is named miR-19a precursor-13 in reference .
2nd Structure of pre-miRNA
Disease
Mature miRNA Information
Mature miRNA hsa-miR-19a-3p
Mature Sequence 49| UGUGCAAAUCUAUGCAAAACUGA |71
Evidence Experimental
Experiments Cloned
Putative hsa-miR-19a-3p 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' agUCAAAACGUAUCUAAACGUGu 5'
            | ||||||  || ||||||| 
Target 5' tgAATTTTGC--AGTTTTGCACa 3'
1211 - 1231 169.00 -15.10
2
miRNA  3' agucaAAACGUAUCU--AAACGUGu 5'
               ||   ||:|:  ||||||| 
Target 5' tgacaTTATAATGGGCTTTTGCACt 3'
2238 - 2262 148.00 -8.80
3
miRNA  3' agucaaaacguaucuAAACGUGu 5'
                         ||||||| 
Target 5' ttcacatcctaccccTTTGCACt 3'
399 - 421 140.00 -5.60
Experimental Support 1 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-19a-3p :: PTEN    [ Functional MTI ]
Validation Method Luciferase reporter assay , Reporter assay
Conditions HeLa
Location of target site 3'UTR
Original Description (Extracted from the article) ... Experimental Support for Predicted Targets.//{These MTI shown in Fig. 3} ...

- Lewis, B. P. Shih, I. H. Jones-Rhoades, M. et al., 2003, Cell.

Article - Lewis, B. P. Shih, I. H. Jones-Rhoades, M. et al.
- Cell, 2003
MicroRNAs (miRNAs) can play important gene regulatory roles in nematodes, insects, and plants by basepairing to mRNAs to specify posttranscriptional repression of these messages. However, the mRNAs regulated by vertebrate miRNAs are all unknown. Here we predict more than 400 regulatory target genes for the conserved vertebrate miRNAs by identifying mRNAs with conserved pairing to the 5' region of the miRNA and evaluating the number and quality of these complementary sites. Rigorous tests using shuffled miRNA controls supported a majority of these predictions, with the fraction of false positives estimated at 31% for targets identified in human, mouse, and rat and 22% for targets identified in pufferfish as well as mammals. Eleven predicted targets (out of 15 tested) were supported experimentally using a HeLa cell reporter system. The predicted regulatory targets of mammalian miRNAs were enriched for genes involved in transcriptional regulation but also encompassed an unexpectedly broad range of other functions.
LinkOut: [PMID: 14697198]
Experimental Support 2 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-19a-3p :: PTEN    [ Functional MTI ]
Validation Method qRT-PCR , Western blot , Other
Conditions 158 patients with CS, CSL, or BRRS
Location of target site 3'UTR
Original Description (Extracted from the article) ... 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. ...

- Pezzolesi, M. G. Platzer, P. Waite, K. A. Eng, C., 2008, Am J Hum Genet.

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 3 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-19a-3p :: PTEN    [ Functional MTI ]
Validation Method Other
Article - Wang, L. Pal, S. Sif, S.
- Mol Cell Biol, 2008
The proper epigenetic modification of chromatin by protein arginine methyltransferases (PRMTs) is crucial for normal cell growth and health. The human SWI/SNF-associated PRMT5 is involved in the transcriptional repression of target genes by directly methylating H3R8 and H4R3. To further understand the impact of PRMT5-mediated histone methylation on cancer, we analyzed its expression in normal and transformed human B lymphocytes. Our findings reveal that PRMT5 protein levels are enhanced in various human lymphoid cancer cells, including transformed chronic lymphocytic leukemia (B-CLL) cell lines. PRMT5 overexpression is caused by the altered expression of the PRMT5-specific microRNAs 19a, 25, 32, 92, 92b, and 96 and results in the increased global symmetric methylation of H3R8 and H4R3. An evaluation of both epigenetic marks at PRMT5 target genes such as RB1 (p105), RBL1 (p107), and RBL2 (p130) showed that promoters H3R8 and H4R3 are hypermethylated, which in turn triggers pocket protein transcriptional repression. Furthermore, reducing PRMT5 expression in WaC3CD5 B-CLL cells abolishes H3R8 and H4R3 hypermethylation, restores RBL2 expression, and inhibits cancer cell proliferation. These results indicate that PRMT5 overexpression epigenetically alters the transcription of key tumor suppressor genes and suggest a causal role of the elevated symmetric methylation of H3R8 and H4R3 at the RBL2 promoter in transformed B-lymphocyte pathology.
LinkOut: [PMID: 18694959]
Experimental Support 4 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-19a-3p :: PTEN    [ Functional MTI ]
Validation Method Luciferase reporter assay
Conditions DU145 , PWR-1E
Location of target site 3'UTR
Tools used in this research miRanda , miRBase Target Database , PicTar , TargetScanS
Original Description (Extracted from the article) ... Direct interaction of miR-17, 19, 22, 25 and 302 with PTEN 3'UTR. ...

- Poliseno, L. Salmena, L. Riccardi, L. et al., 2010, Sci Signal.

miRNA-target interactions (Provided by authors)
IDDuplex structurePosition
1
miRNA  3' agUCAAAACGUAUCUAAACGUGu 5'
            | ||||||  || ||||||| 
Target 5' tgAATTTTGC--AGTTTTGCAC- 3'
3 - 22
Article - Poliseno, L. Salmena, L. Riccardi, L. et al.
- Sci Signal, 2010
PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a tumor suppressor that antagonizes signaling through the phosphatidylinositol 3-kinase-Akt pathway. We have demonstrated that subtle decreases in PTEN abundance can have critical consequences for tumorigenesis. Here, we used a computational approach to identify miR-22, miR-25, and miR-302 as three PTEN-targeting microRNA (miRNA) families found within nine genomic loci. We showed that miR-22 and the miR-106b~25 cluster are aberrantly overexpressed in human prostate cancer, correlate with abundance of the miRNA processing enzyme DICER, and potentiate cellular transformation both in vitro and in vivo. We demonstrated that the intronic miR-106b~25 cluster cooperates with its host gene MCM7 in cellular transformation both in vitro and in vivo, so that the concomitant overexpression of MCM7 and the miRNA cluster triggers prostatic intraepithelial neoplasia in transgenic mice. Therefore, the MCM7 gene locus delivers two simultaneous oncogenic insults when amplified or overexpressed in human cancer. Thus, we have uncovered a proto-oncogenic miRNA-dependent network for PTEN regulation and defined the MCM7 locus as a critical factor in initiating prostate tumorigenesis.
LinkOut: [PMID: 20388916]
Experimental Support 5 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-19a-3p :: PTEN    [ Functional MTI ]
Validation Method Luciferase reporter assay , qRT-PCR , Western blot
Conditions MDR human breast cancer cell lines, MCF-7/TX200, MCF-7/VP-16, MCF-7/MX100 and wild-type MCF-7 (MCF7/WT)
Disease multidrug resistance (MDR) of breast cancer cells
Location of target site 3'UTR
Tools used in this research TargetScan
Original Description (Extracted from the article) ... MiR-19 Directly Targets PTEN ...

- Liang, Z. Li, Y. Huang, K. Wagar, N. Shim, H., 2011, Pharm Res.

Article - Liang, Z. Li, Y. Huang, K. Wagar, N. Shim, H.
- Pharm Res, 2011
PURPOSE: To explore whether miR-19 is involved in the regulation of multidrug resistance (MDR), one of the main causes of breast cancer mortality, and modulates sensitivity of tumor cells to chemotherapeutic agents. METHODS: We analyzed miRNA expression levels in three MDR cell lines in comparison with their parent cell line, MCF-7, using a miRNA microarray. We investigated whether inhibitor of miR-19 sensitized MDR cells to chemotherapeutic agents in vitro and in vivo. RESULTS: MiR-19 was overexpressed in all three MDR cell lines compared to their parental cell line, MCF-7. Expression levels of miR-19 in MDR cells were inversely consistent with those of PTEN. Inhibitor of miR-19a restored sensitivity of MDR cells to cytotoxic agents; administration of LNA-antimiR-19a, a chemo-modified miR-19a inhibitor, sensitized MDR cells to chemotherapeutic agents in vivo. CONCLUSION: Our findings demonstrate, for the first time, involvement of miR-19 in multidrug resistance through modulation of PTEN and suggest that miR-19 may be a potential target for preventing and reversing MDR in tumor cells.
LinkOut: [PMID: 21853360]
MiRNA-Target Expression Profile:

 
MiRNA-Target Interaction Network:
Strong evidence (reporter assay, western blot, qRT-PCR or qPCR)
Other evidence
39 hsa-miR-19a-3p Target Genes:
ID Target Description Validation methods
Strong evidence Less strong evidence
MIRT001794 HOXA5 homeobox A5 2 2
MIRT001795 MECP2 methyl CpG binding protein 2 (Rett syndrome) 3 2
MIRT002958 PTEN phosphatase and tensin homolog 4 5
MIRT003214 ESR1 estrogen receptor 1 4 2
MIRT003426 CCND1 cyclin D1 5 3
MIRT003533 ERBB4 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) 3 3
MIRT003536 NR4A2 nuclear receptor subfamily 4, group A, member 2 3 3
MIRT003781 ATXN1 ataxin 1 4 3
MIRT004334 KAT2B K(lysine) acetyltransferase 2B 3 2
MIRT004337 SOCS1 suppressor of cytokine signaling 1 3 3
MIRT004350 PRMT5 protein arginine methyltransferase 5 2 2
MIRT004452 BCL2L11 BCL2-like 11 (apoptosis facilitator) 2 5
MIRT004593 TGFBR2 transforming growth factor, beta receptor II (70/80kDa) 3 3
MIRT004934 BMPR2 bone morphogenetic protein receptor, type II (serine/threonine kinase) 4 3
MIRT005396 ARIH2 ariadne homolog 2 (Drosophila) 2 2
MIRT005630 SMAD4 SMAD family member 4 3 2
MIRT006179 KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog 4 1
MIRT006475 CUL5 cullin 5 2 1
MIRT006646 TLR2 toll-like receptor 2 3 1
MIRT006787 TNF tumor necrosis factor 1 1
MIRT007118 SUZ12 suppressor of zeste 12 homolog (Drosophila) 1 1
MIRT007119 RAB13 RAB13, member RAS oncogene family 1 1
MIRT007120 MSMO1 sterol-C4-methyl oxidase-like 1 1
MIRT007121 ABCA1 ATP-binding cassette, sub-family A (ABC1), member 1 1 1
MIRT007122 PSAP prosaposin 1 1
MIRT031304 THBS1 thrombospondin 1 1 1
MIRT031305 CTGF connective tissue growth factor 1 1
MIRT031306 DPYSL2 dihydropyrimidinase-like 2 1 1
MIRT031307 VPS4B vacuolar protein sorting 4 homolog B (S. cerevisiae) 1 1
MIRT031308 MYCN v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian) 1 1
MIRT031309 RAB14 RAB14, member RAS oncogene family 1 1
MIRT050641 KDELR2 KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 2 1 1
MIRT050642 RNF4 ring finger protein 4 1 1
MIRT050643 PRRC2C HLA-B associated transcript 2-like 2 1 1
MIRT050644 TMEM87A transmembrane protein 87A 1 1
MIRT050645 MTF2 metal response element binding transcription factor 2 1 1
MIRT050646 GRK6 G protein-coupled receptor kinase 6 1 1
MIRT050647 RPS6KA5 ribosomal protein S6 kinase, 90kDa, polypeptide 5 1 1
MIRT050648 WDFY3 WD repeat and FYVE domain containing 3 1 1