Accession ID: MIRT000799 [miRNA, hsa-miR-214 :: PTEN, target gene]
pre-miRNA Information
pre-miRNA ID hsa-mir-214 LinkOut: [miRBase ]
Synonyms MIRN214, miRNA214, mir-214, MIR214
Description Homo sapiens miR-214 stem-loop
Comment This human miRNA was predicted by computational methods using conservation with mouse and Fugu rubripes sequences .
2nd Structure of pre-miRNA
Mature miRNA Information
Mature miRNA hsa-miR-214-3p
Mature Sequence 71| ACAGCAGGCACAGACAGGCAGU |92
Evidence Experimental
Experiments Cloned
Putative hsa-miR-214-3p Targets LinkOut: [ TargetScanS 5.1 | MicroCosm | microRNA.org | miRecords | miRDB | miRo | miRNAMap 2.0 ]
Mature miRNA hsa-miR-214-5p
Mature Sequence 30| UGCCUGUCUACACUUGCUGUGC |51
Evidence Experimental
Experiments Cloned
Putative hsa-miR-214-5p Targets LinkOut: [ TargetScanS 5.1 | MicroCosm | microRNA.org | miRecords | miRDB | miRo | miRNAMap 2.0 ]
miRNA-target interaction network
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_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)
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
miRNA-target interactions (Predicted by miRanda)
IDDuplex structurePositionScoreMFE
1
miRNA  3' ugacggacagacACGGACGACa 5'
                      | ||||||| 
Target 5' tttcaatcataaTACCTGCTGt 3'
1003 - 1024 142.00 -13.30
2
miRNA  3' ugacgGACAGACACGGACGACa 5'
               |||||  |||:||:|| 
Target 5' ggccgCTGTCACTGCTTGTTGt 3'
632 - 653 137.00 -18.80
3
miRNA  3' ugACGGA-CAGAC-ACGGACGaca 5'
            |||:|  | || |||||||   
Target 5' gaTGCTTCATGTGCTGCCTGCaag 3'
1026 - 1049 124.00 -14.42
Experimental Support 1 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-214 :: PTEN    [ Functional MTI ]
Validation Method Western blot , qRT-PCR , Luciferase reporter assay
Conditions HIOSE, A2780CP,
Location of target site 3'UTR, unknown
Original Description (Extracted from the article) ... Significantly, miR-214 induces cell survival and cisplatin resistance through targeting the 3'-untranslated region (UTR) of the PTEN, which leads to down-regulation of PTEN protein and activation of Akt pathway. ...

- Yang, H. Kong, W. He, L. Zhao, J. J. et al., 2008, Cancer Res.

Article - Yang, H. Kong, W. He, L. Zhao, J. J. et al.
- Cancer Res, 2008
MicroRNAs (miRNA) represent a novel class of genes that function as negative regulators of gene expression. Recently, miRNAs have been implicated in several cancers. However, aberrant miRNA expression and its clinicopathologic significance in human ovarian cancer have not been well documented. Here, we show that several miRNAs are altered in human ovarian cancer, with the most significantly deregulated miRNAs being miR-214, miR-199a*, miR-200a, miR-100, miR-125b, and let-7 cluster. Further, we show the frequent deregulation of miR-214, miR-199a*, miR-200a, and miR-100 in ovarian cancers. Significantly, miR-214 induces cell survival and cisplatin resistance through targeting the 3'-untranslated region (UTR) of the PTEN, which leads to down-regulation of PTEN protein and activation of Akt pathway. Inhibition of Akt using Akt inhibitor, API-2/triciribine, or introduction of PTEN cDNA lacking 3'-UTR largely abrogates miR-214-induced cell survival. These findings indicate that deregulation of miRNAs is a recurrent event in human ovarian cancer and that miR-214 induces cell survival and cisplatin resistance primarily through targeting the PTEN/Akt pathway.
LinkOut: [PMID: 18199536]
Experimental Support 2 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-214 :: PTEN    [ Functional MTI ]
Validation Method Luciferase reporter assay , Microarray , qRT-PCR , Western blot
Conditions HIO80
Location of target site 3'UTR
Original Description (Extracted from the article) ... In vivo, transcripts containing the 39 untranslated region of Pten, including the miR-214 target sequence, were negatively regulated after T cell activation, and forced expression of miR-214 in T cells led to increased pro- liferation after stimulation.// ...

- Jindra, P. T. Bagley, J. Godwin, J. G. et al., 2010, J Immunol.

Article - Jindra, P. T. Bagley, J. Godwin, J. G. et al.
- J Immunol, 2010
T cell activation requires signaling through the TCR and costimulatory molecules, such as CD28. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression posttranscriptionally and are also known to be involved in lymphocyte development and function. In this paper, we set out to examine potential roles of miRNAs in T cell activation, using genome-wide expression profiling to identify miRNAs differentially regulated following T cell activation. One of the miRNAs upregulated after T cell activation, miR-214, was predicted to be capable of targeting Pten based on bioinformatics and reports suggesting that it targets Pten in ovarian tumor cells. Upregulation of miR-214 in T cells inversely correlated with levels of phosphatase and tensin homolog deleted on chromosome 10. In vivo, transcripts containing the 3' untranslated region of Pten, including the miR-214 target sequence, were negatively regulated after T cell activation, and forced expression of miR-214 in T cells led to increased proliferation after stimulation. Blocking CD28 signaling in vivo prevented miR-214 upregulation in alloreactive T cells. Stimulation of T cells through the TCR alone was not sufficient to result in upregulation of miR-214. Thus, costimulation-dependent upregulation of miR-214 promotes T cell activation by targeting the negative regulator Pten. Thus, the requirement for T cell costimulation is, in part, related to its ability to regulate expression of miRNAs that control T cell activation.
LinkOut: [PMID: 20548023]
Experimental Support 3 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-214 :: PTEN    [ Functional MTI ]
Validation Method Luciferase reporter assay , qRT-PCR , Western blot
Conditions THP 1
Location of target site 3'UTR
Tools used in this research miRanda, PicTar, TargetScan
Original Description (Extracted from the article) ... the current study demonstrated a distinctive miRNA-expression pattern in AGE-treated monocytes and a novel role for miR-214–targeting PTEN in AGE-induced monocyte resistance to apoptosis. Identification of the miR-214–targeting PTEN pathway in the modulation of monocytic apoptosis provides a potential new therapeutic target in the treatment of inflammatory disease. ...

- Li, L. M. Hou, D. X. Guo, Y. L. Yang, J. W. et al., 2011, Journal of immunology.

miRNA-target interactions (Provided by authors)
IDDuplex structurePosition
1
miRNA  3' ugacggacagacACGGACGACa 5'
                      | ||||||| 
Target 5' uuucaaucauaaUACCUGCUGu 3'
2 - 23
Article - Li, L. M. Hou, D. X. Guo, Y. L. Yang, J. W. et al.
- Journal of immunology, 2011
Advanced glycation end products (AGEs) delay spontaneous apoptosis of monocytes and contribute to the development of inflammatory responses. However, the mechanism by which AGEs affect monocyte apoptosis is unclear. We studied the role of microRNA-214 (miR-214) and its target gene in AGE-induced monocytic apoptosis delay. Using microRNA (miRNA) microarray and stem-loop, quantitative RT-PCR assay, we studied genome-wide miRNA expression in THP-1 cells treated with or without AGEs. Significant upregulation of miR-214 was consistently observed in THP-1 and human monocytes treated with various AGEs, and AGE-induced monocytic miR-214 upregulation was likely through activation of receptor for AGEs. A striking increase in miR-214 was also detected in monocytes from patients with chronic renal failure. Luciferase reporter assay showed that miR-214 specifically binds to the phosphatase and tensin homolog (PTEN) mRNA 3'-untranslated region, implicating PTEN as a target gene of miR-214. PTEN expression is inversely correlated with miR-214 level in monocytes. Compared with normal monocytes, AGE-treated monocytes and monocytes from chronic renal failure patients exhibited lower PTEN levels and delayed apoptosis. Overexpression of pre-miR-214 led to impaired PTEN expression and delayed apoptosis of THP-1 cells, whereas knockdown of miR-214 level largely abolished AGE-induced cell survival. Our findings define a new role for miR-214-targeting PTEN in AGE-induced monocyte survival.
LinkOut: [PMID: 21228352]