Accession ID: MIRT000533 [miRNA, hsa-miR-217 :: PTEN, target gene]
pre-miRNA Information
pre-miRNA ID hsa-mir-217LinkOut: [miRBase ]
Synonyms MIRN217, mir-217, MIR217
Description Homo sapiens miR-217 stem-loop
Comment This human miRNA was predicted by computational methods using conservation with mouse and Fugu rubripes sequences .
2nd Structure of pre-miRNA
Disease
Mature miRNA Information
Mature miRNA hsa-miR-217
Mature Sequence 35| UACUGCAUCAGGAACUGAUUGGA |57
Evidence Experimental
Experiments Cloned
Putative hsa-miR-217 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, GLM2, MHAM, MMAC1, PTEN1, TEP1
Description phosphatase and tensin homolog
Transcript NM_000314    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_000314|3'UTR
   1 ATTTTTTTTTATCAAGAGGGATAAAACACCATGAAAATAAACTTGAATAAACTGAAAATGGACCTTTTTTTTTTTAATGG
  81 CAATAGGACATTGTGTCAGATTACCAGTTATAGGAACAATTCTCTTTTCCTGACCAATCTTGTTTTACCCTATACATCCA
 161 CAGGGTTTTGACACTTGTTGTCCAGTTGAAAAAAGGTTGTGTAGCTGTGTCATGTATATACCTTTTTGTGTCAAAAGGAC
 241 ATTTAAAATTCAATTAGGATTAATAAAGATGGCACTTTCCCGTTTTATTCCAGTTTTATAAAAAGTGGAGACAGACTGAT
 321 GTGTATACGTAGGAATTTTTTCCTTTTGTGTTCTGTCACCAACTGAAGTGGCTAAAGAGCTTTGTGATATACTGGTTCAC
 401 ATCCTACCCCTTTGCACTTGTGGCAACAGATAAGTTTGCAGTTGGCTAAGAGAGGTTTCCGAAGGGTTTTGCTACATTCT
 481 AATGCATGTATTCGGGTTAGGGGAATGGAGGGAATGCTCAGAAAGGAAATAATTTTATGCTGGACTCTGGACCATATACC
 561 ATCTCCAGCTATTTACACACACCTTTCTTTAGCATGCTACAGTTATTAATCTGGACATTCGAGGAATTGGCCGCTGTCAC
 641 TGCTTGTTGTTTGCGCATTTTTTTTTAAAGCATATTGGTGCTAGAAAAGGCAGCTAAAGGAAGTGAATCTGTATTGGGGT
 721 ACAGGAATGAACCTTCTGCAACATCTTAAGATCCACAAATGAAGGGATATAAAAATAATGTCATAGGTAAGAAACACAGC
 801 AACAATGACTTAACCATATAAATGTGGAGGCTATCAACAAAGAATGGGCTTGAAACATTATAAAAATTGACAATGATTTA
 881 TTAAATATGTTTTCTCAATTGTAACGACTTCTCCATCTCCTGTGTAATCAAGGCCAGTGCTAAAATTCAGATGCTGTTAG
 961 TACCTACATCAGTCAACAACTTACACTTATTTTACTAGTTTTCAATCATAATACCTGCTGTGGATGCTTCATGTGCTGCC
1041 TGCAAGCTTCTTTTTTCTCATTAAATATAAAATATTTTGTAATGCTGCACAGAAATTTTCAATTTGAGATTCTACAGTAA
1121 GCGTTTTTTTTCTTTGAAGATTTATGATGCACTTATTCAATAGCTGTCAGCCGTTCCACCCTTTTGACCTTACACATTCT
1201 ATTACAATGAATTTTGCAGTTTTGCACATTTTTTAAATGTCATTAACTGTTAGGGAATTTTACTTGAATACTGAATACAT
1281 ATAATGTTTATATTAAAAAGGACATTTGTGTTAAAAAGGAAATTAGAGTTGCAGTAAACTTTCAATGCTGCACACAAAAA
1361 AAAGACATTTGATTTTTCAGTAGAAATTGTCCTACATGTGCTTTATTGATTTGCTATTGAAAGAATAGGGTTTTTTTTTT
1441 TTTTTTTTTTTTTTTTTTTAAATGTGCAGTGTTGAATCATTTCTTCATAGTGCTCCCCCGAGTTGGGACTAGGGCTTCAA
1521 TTTCACTTCTTAAAAAAAATCATCATATATTTGATATGCCCAGACTGCATACGATTTTAAGCGGAGTACAACTACTATTG
1601 TAAAGCTAATGTGAAGATATTATTAAAAAGGTTTTTTTTTCCAGAAATTTGGTGTCTTCAAATTATACCTTCACCTTGAC
1681 ATTTGAATATCCAGCCATTTTGTTTCTTAATGGTATAAAATTCCATTTTCAATAACTTATTGGTGCTGAAATTGTTCACT
1761 AGCTGTGGTCTGACCTAGTTAATTTACAAATACAGATTGAATAGGACCTACTAGAGCAGCATTTATAGAGTTTGATGGCA
1841 AATAGATTAGGCAGAACTTCATCTAAAATATTCTTAGTAAATAATGTTGACACGTTTTCCATACCTTGTCAGTTTCATTC
1921 AACAATTTTTAAATTTTTAACAAAGCTCTTAGGATTTACACATTTATATTTAAACATTGATATATAGAGTATTGATTGAT
2001 TGCTCATAAGTTAAATTGGTAAAGTTAGAGACAACTATTCTAACACCTCACCATTGAAATTTATATGCCACCTTGTCTTT
2081 CATAAAAGCTGAAAATTGTTACCTAAAATGAAAATCAACTTCATGTTTTGAAGATAGTTATAAATATTGTTCTTTGTTAC
2161 AATTTCGGGCACCGCATATTAAAACGTAACTTTATTGTTCCAATATGTAACATGGAGGGCCAGGTCATAAATAATGACAT
2241 TATAATGGGCTTTTGCACTGTTATTATTTTTCCTTTGGAATGTGAAGGTCTGAATGAGGGTTTTGATTTTGAATGTTTCA
2321 ATGTTTTTGAGAAGCCTTGCTTACATTTTATGGTGTAGTCATTGGAAATGGAAAAATGGCATTATATATATTATATATAT
2401 AAATATATATTATACATACTCTCCTTACTTTATTTCAGTTACCATCCCCATAGAATTTGACAAGAATTGCTATGACTGAA
2481 AGGTTTTCGAGTCCTAATTAAAACTTTATTTATGGCAGTATTCATAATTAGCCTGAAATGCATTCTGTAGGTAATCTCTG
2561 AGTTTCTGGAATATTTTCTTAGACTTTTTGGATGTGCAGCAGCTTACATGTCTGAAGTTACTTGAAGGCATCACTTTTAA
2641 GAAAGCTTACAGTTGGGCCCTGTACCATCCCAAGTCCTTTGTAGCTCCTCTTGAACATGTTTGCCATACTTTTAAAAGGG
2721 TAGTTGAATAAATAGCATCACCATTCTTTGCTGTGGCACAGGTTATAAACTTAAGTGGAGTTTACCGGCAGCATCAAATG
2801 TTTCAGCTTTAAAAAATAAAAGTAGGGTACAAGTTTAATGTTTAGTTCTAGAAATTTTGTGCAATATGTTCATAACGATG
2881 GCTGTGGTTGCCACAAAGTGCCTCGTTTACCTTTAAATACTGTTAATGTGTCATGCATGCAGATGGAAGGGGTGGAACTG
2961 TGCACTAAAGTGGGGGCTTTAACTGTAGTATTTGGCAGAGTTGCCTTCTACCTGCCAGTTCAAAAGTTCAACCTGTTTTC
3041 ATATAGAATATATATACTAAAAAATTTCAGTCTGTTAAACAGCCTTACTCTGATTCAGCCTCTTCAGATACTCTTGTGCT
3121 GTGCAGCAGTGGCTCTGTGTGTAAATGCTATGCACTGAGGATACACAAAAATACCAATATGATGTGTACAGGATAATGCC
3201 TCATCCCAATCAGATGTCCATTTGTTATTGTGTTTGTTAACAACCCTTTATCTCTTAGTGTTATAAACTCCACTTAAAAC
3281 TGATTAAAGTCTCATTCTTGTCA
Target sites Provided by authors  Predicted by miRanda
miRNA-target interactions (Predicted by miRanda)
IDDuplex structurePositionScoreMFE
1
miRNA  3' agGUUAGUCA-AGGAC-UACGUCau 5'
            :|||  || || || ||||||  
Target 5' gtTAAT--GTGTCATGCATGCAGat 3'
2922 - 2944 137.00 -8.60
2
miRNA  3' agGUUAGUCAAGGAC--UACGUCAu 5'
            :|||:||  ||||  ||||| | 
Target 5' caTAATTAG--CCTGAAATGCATTc 3'
2523 - 2545 135.00 -12.02
3
miRNA  3' agguuaGUCAAGGACUACGUCAu 5'
                || ||: ||:||:||| 
Target 5' tgcttaCATTTTATGGTGTAGTc 3'
2338 - 2360 133.00 -10.90
Experimental Support 1 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-217 :: PTEN    [ Functional MTI ]
Validation Method Other
Article - Kato, M. Putta, S. Wang, M. Yuan, H. et al.
- Nat Cell Biol, 2009
Akt kinase is activated by transforming growth factor-beta1 (TGF-beta) in diabetic kidneys, and has important roles in fibrosis, hypertrophy and cell survival in glomerular mesangial cells. However, the mechanisms of Akt activation by TGF-beta are not fully understood. Here we show that TGF-beta activates Akt in glomerular mesangial cells by inducing the microRNAs (miRNAs) miR-216a and miR-217, both of which target PTEN (phosphatase and tensin homologue), an inhibitor of Akt activation. These miRNAs are located within the second intron of a non-coding RNA (RP23-298H6.1-001). The RP23 promoter was activated by TGF-beta and miR-192 through E-box-regulated mechanisms, as shown previously. Akt activation by these miRs led to glomerular mesangial cell survival and hypertrophy, which were similar to the effects of activation by TGF-beta. These studies reveal a mechanism of Akt activation through PTEN downregulation by two miRs, which are regulated by upstream miR-192 and TGF-beta. Due to the diversity of PTEN function, this miR-amplifying circuit may have key roles, not only in kidney disorders, but also in other diseases.
LinkOut: [PMID: 19543271]
Experimental Support 2 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-217 :: PTEN    [ Functional MTI ]
Validation Method Luciferase reporter assay , Western blot , Other
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 3 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-217 :: PTEN    [ Functional MTI ]
Validation Method Luciferase reporter assay
Conditions PLC/PRF/5
Location of target site 3'UTR
Tools used in this research miRecord
Original Description (Extracted from the article) ... SMAD7 and PTEN are identified as two functional downstream targets of miR-216a /217 ...

- Xia, H. Ooi, L. L. Hui, K. M., 2013, Hepatology.

miRNA-target interactions (Provided by authors)
IDDuplex structurePosition
1
miRNA  3' aggUUAGUCAAGGACUACGUCAu 5'
             |||:||     | |||||| 
Target 5' ggaAAUUAG----AGUUGCAGUa 3'
6 - 24
Article - Xia, H. Ooi, L. L. Hui, K. M.
- Hepatology, 2013
Tumor recurrence and metastases are the major obstacles to improving the prognosis of patients with hepatocellular carcinoma (HCC). To identify novel risk factors associated with HCC recurrence and metastases, we have established a panel of recurrence-associated microRNAs by comparing the microRNA expression in recurrent and non-recurrent human HCC tissue samples using microarrays (recurrence is defined as recurrent disease occurring within a 2-year time point of the original treatment). Among the panel, expression of the miR-216a/217 cluster was consistently and significantly upregulated in HCC tissue samples and cell lines associated with early tumor recurrence, poor disease-free survival and an epithelial-mesenchymal transition (EMT) phenotype. Stable over-expression of miR-216a/217-induced EMT, increased the stemlike cell population, migration and metastatic ability of epithelial HCC cells. PTEN and SMAD7 were subsequently identified as two functional targets of miR-216a/217, and both PTEN and SMAD7 were downregulated in HCC. Ectopic expression of PTEN or SMAD7 partially rescued miR-216a/217-mediated EMT, cell migration and stem-like properties of HCC cells. Previously, SMAD7 was shown to be a TGF-beta type 1 receptor antagonist. Here, we further demonstrated that the overexpression of miR-216a/217 acted as a positive feedback regulator for the TGF-beta pathway and the canonical pathway involved in the activation of PI3K/Akt signaling in HCC cells. Additionally, activation of the TGF-beta and PI3K/Akt signaling pathways in HCC cells resulted in an acquired resistance to sorafenib, while blocking the activation of TGF-beta pathway overcame miR-216a/217-induced sorafenib resistance and prevented tumor metastases in HCC. Conclusion: our present study demonstrates that overexpression of miR-216a/217 activates the PI3K/Akt and TGF-beta pathways by targeting PTEN and SMAD7, contributing to hepatocarcinogenesis and tumor recurrence in HCC. (HEPATOLOGY 2013.).
LinkOut: [PMID: 23471579]
MiRNA-Target Expression Profile:

 
MiRNA-Target Expression Profile(TCGA):

 
MiRNA-Target Interaction Network:
Strong evidence (reporter assay, western blot, qRT-PCR or qPCR)
Other evidence
67 hsa-miR-217 Target Genes:
ID Target Description Validation methods
Strong evidence Less strong evidence
MIRT000144 SIRT1 sirtuin 1 4 2
MIRT000481 ROBO1 roundabout, axon guidance receptor, homolog 1 (Drosophila) 4 1
MIRT000533 PTEN phosphatase and tensin homolog 3 3
MIRT003535 NR4A2 nuclear receptor subfamily 4, group A, member 2 3 1
MIRT004010 EZH2 enhancer of zeste homolog 2 (Drosophila) 4 2
MIRT004866 TRAPPC2P1 trafficking protein particle complex 2 pseudogene 1 2 1
MIRT005685 PPM1D protein phosphatase, Mg2+/Mn2+ dependent, 1D 1 1
MIRT006363 FHIT fragile histidine triad 1 1
MIRT006501 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 1 1
MIRT007153 SMAD7 SMAD family member 7 1 1
MIRT024253 Pten phosphatase and tensin homolog 1 1
MIRT024254 IRS1 insulin receptor substrate 1 1 1
MIRT053154 E2F3 E2F transcription factor 3 2 1
MIRT054838 DACH1 dachshund homolog 1 (Drosophila) 3 1
MIRT097003 MAP1B microtubule-associated protein 1B 1 1
MIRT226550 TP53INP1 tumor protein p53 inducible nuclear protein 1 1 1
MIRT243450 LMLN leishmanolysin-like (metallopeptidase M8 family) 1 1
MIRT270975 FLVCR1 feline leukemia virus subgroup C cellular receptor 1 1 1
MIRT271119 ZNF268 zinc finger protein 268 1 2
MIRT315221 FOXO3 forkhead box O3 3 1
MIRT331090 GHITM growth hormone inducible transmembrane protein 1 1
MIRT349300 ZNF317 zinc finger protein 317 1 1
MIRT438314 GPC5 glypican 5 3 1
MIRT443492 ZNF583 zinc finger protein 583 1 1
MIRT445834 SRSF11 serine/arginine-rich splicing factor 11 1 1
MIRT462007 SNRNP27 small nuclear ribonucleoprotein 27kDa (U4/U6.U5) 1 1
MIRT488451 ACBD3 acyl-CoA binding domain containing 3 1 1
MIRT496632 TMEM67 transmembrane protein 67 1 1
MIRT502218 HSPA4L heat shock 70kDa protein 4-like 1 2
MIRT505421 TCF7L2 transcription factor 7-like 2 (T-cell specific, HMG-box) 1 2
MIRT508428 SFTPB surfactant protein B 1 1
MIRT513125 OSBPL3 oxysterol binding protein-like 3 1 1
MIRT521500 RAB11B RAB11B, member RAS oncogene family 1 1
MIRT532484 HOXA13 homeobox A13 1 1
MIRT533643 TMSB4X thymosin beta 4, X-linked 1 1
MIRT533938 TAF1D TATA box binding protein (TBP)-associated factor, RNA polymerase I, D, 41kDa 1 1
MIRT539384 ADSS adenylosuccinate synthase 1 3
MIRT546247 TNFRSF21 tumor necrosis factor receptor superfamily, member 21 1 1
MIRT547978 HIF1A hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) 1 1
MIRT550850 TMEM63A transmembrane protein 63A 1 1
MIRT555488 PNRC2 proline-rich nuclear receptor coactivator 2 1 1
MIRT558575 CREBZF CREB/ATF bZIP transcription factor 1 1
MIRT575909 March5 membrane-associated ring finger (C3HC4) 5 1 1
MIRT610752 MARCH5 membrane-associated ring finger (C3HC4) 5 1 3
MIRT613152 DNAL1 dynein, axonemal, light chain 1 1 1
MIRT624598 BACH2 BTB and CNC homology 1, basic leucine zipper transcription factor 2 1 1
MIRT630875 UBXN11 UBX domain protein 11 1 1
MIRT639314 CKAP4 cytoskeleton-associated protein 4 1 1
MIRT639870 STK40 serine/threonine kinase 40 1 1
MIRT641783 ZBTB20 zinc finger and BTB domain containing 20 1 1
MIRT645976 NHLRC2 NHL repeat containing 2 1 1
MIRT648474 TCERG1 transcription elongation regulator 1 1 1
MIRT648798 VPS8 vacuolar protein sorting 8 homolog (S. cerevisiae) 1 1
MIRT652845 TACO1 translational activator of mitochondrially encoded cytochrome c oxidase I 1 1
MIRT682748 CA6 carbonic anhydrase VI 1 1
MIRT683723 LACTB lactamase, beta 1 1
MIRT701707 MXD1 MAX dimerization protein 1 1 1
MIRT701913 MMGT1 membrane magnesium transporter 1 1 1
MIRT704818 CDC73 cell division cycle 73, Paf1/RNA polymerase II complex component, homolog (S. cerevisiae) 1 1
MIRT705207 BTG1 B-cell translocation gene 1, anti-proliferative 1 1
MIRT709727 FAM196B family with sequence similarity 196, member B 1 1
MIRT711160 WDR82P1 WD repeat domain 82 pseudogene 1 1 1
MIRT713022 SLC4A2 solute carrier family 4, anion exchanger, member 2 (erythrocyte membrane protein band 3-like 1) 1 1
MIRT718754 ZNF490 zinc finger protein 490 1 1
MIRT719493 LSG1 large subunit GTPase 1 homolog (S. cerevisiae) 1 1
MIRT720644 ELF5 E74-like factor 5 (ets domain transcription factor) 1 1
MIRT723026 HINFP histone H4 transcription factor 1 1
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