Accession ID: MIRT005586 [miRNA, hsa-miR-222 :: PTEN, target gene]
|Synonyms||MIRN222, miRNA222, mir-222, MIR222|
|Description||Homo sapiens miR-222 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 Sequence||69| AGCUACAUCUGGCUACUGGGU |89|
|Putative hsa-miR-222-3p Targets|
|Mature Sequence||31| CUCAGUAGCCAGUGUAGAUCCU |52|
|Putative hsa-miR-222-5p Targets|
|Synonyms||10q23del, BZS, DEC, MGC11227, MHAM, MMAC1, PTEN1, TEP1|
|Description||phosphatase and tensin homolog|
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|
|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
|miRNA-target interactions (Predicted by miRanda)||
|miRNA:Target||hsa-miR-222 :: PTEN [ Functional MTI ]|
|Validation Method||Flow , Immunohistochemistry , Luciferase reporter assay , qRT-PCR , Western blot|
|Conditions||H460, CALU 1|
|Location of target site||3'UTR|
|Original Description (Extracted from the article)||... MiR-221 and miR-222 Directly Target PTEN and TIMP3 3'UTRs. ...
- Garofalo, M. Di Leva, G. Romano, G. Nuovo, et al., 2009, Cancer Cell.
|miRNA-target interactions (Provided by authors)||
miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation- Garofalo, M. Di Leva, G. Romano, G. Nuovo, et al.
- Cancer Cell, 2009
Lung and liver cancers are among the most deadly types of cancer. Despite improvements in treatment over the past few decades, patient survival remains poor, underlining the need for development of targeted therapies. MicroRNAs represent a class of small RNAs frequently deregulated in human malignancies. We now report that miR-221&222 are overexpressed in aggressive non-small cell lung cancer and hepatocarcinoma cells, as compared with less invasive and/or normal lung and liver cells. We show that miR-221&222, by targeting PTEN and TIMP3 tumor suppressors, induce TRAIL resistance and enhance cellular migration through the activation of the AKT pathway and metallopeptidases. Finally, we demonstrate that the MET oncogene is involved in miR-221&222 activation through the c-Jun transcription factor.LinkOut: [PMID: 19962668]
|miRNA:Target||hsa-miR-222 :: PTEN [ Functional MTI ]|
|Validation Method||FACS , Flow , Luciferase reporter assay , Northern blot , Western blot|
|Location of target site||3'UTR|
|Tools used in this research||PicTar|
|Original Description (Extracted from the article)||... Notably, the seed sequence of miR-221 and miR-222 matched the 3'UTR of PTEN, and introducing a PTEN cDNA without the 3'UTR into SGC7901 cells abrogated the miR-221 and miR-222-induced malignant phenotype. PTEN-3'UTR luciferase reporter assay confirmed PTEN as a direct target of miR-221 and miR-222.// ...
- Chun-Zhi, Z. Lei, H. An-Ling, Z. Yan-Chao, et al., 2010, BMC Cancer.
MicroRNA-221 and microRNA-222 regulate gastric carcinoma cell proliferation and radioresistance by targeting PTEN- Chun-Zhi, Z. Lei, H. An-Ling, Z. Yan-Chao, et al.
- BMC Cancer, 2010
BACKGROUND: MicroRNAs (miRNAs) can function as either oncogenes or tumor suppressor genes via regulation of cell proliferation and/or apoptosis. MiR-221 and miR-222 were discovered to induce cell growth and cell cycle progression via direct targeting of p27 and p57 in various human malignancies. However, the roles of miR-221 and miR-222 have not been reported in human gastric cancer. In this study, we examined the impact of miR-221 and miR-222 on human gastric cancer cells, and identified target genes for miR-221 and miR-222 that might mediate their biology. METHODS: The human gastric cancer cell line SGC7901 was transfected with AS-miR-221/222 or transduced with pMSCV-miR-221/222 to knockdown or restore expression of miR-221 and miR-222, respectively. The effects of miR-221 and miR-222 were then assessed by cell viability, cell cycle analysis, apoptosis, transwell, and clonogenic assay. Potential target genes were identified by Western blot and luciferase reporter assay. RESULTS: Upregulation of miR-221 and miR-222 induced the malignant phenotype of SGC7901 cells, whereas knockdown of miR-221 and miR-222 reversed this phenotype via induction of PTEN expression. In addition, knockdonwn of miR-221 and miR-222 inhibited cell growth and invasion and increased the radiosensitivity of SGC7901 cells. Notably, the seed sequence of miR-221 and miR-222 matched the 3'UTR of PTEN, and introducing a PTEN cDNA without the 3'UTR into SGC7901 cells abrogated the miR-221 and miR-222-induced malignant phenotype. PTEN-3'UTR luciferase reporter assay confirmed PTEN as a direct target of miR-221 and miR-222. CONCLUSION: These results demonstrate that miR-221 and miR-222 regulate radiosensitivity, and cell growth and invasion of SGC7901 cells, possibly via direct modulation of PTEN expression. Our study suggests that inhibition of miR-221 and miR-222 might form a novel therapeutic strategy for human gastric cancer.LinkOut: [PMID: 20618998]