MicroRNA-34a modulates c-Myc transcriptional complexes to suppress malignancy in human prostate cancer cells.
MicroRNA-34a (miR-34a), a potent mediator of tumor suppressor p53, has been reported to function as a tumor suppressor and miR-34a was found to be downregulated in prostate cancer tissues. We studied the functional effects of miR-34a on c-Myc transcriptional complexes in PC-3 prostate cancer cells....
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3250472?pdf=render |
| _version_ | 1819169422159380480 |
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| author | Soichiro Yamamura Sharanjot Saini Shahana Majid Hiroshi Hirata Koji Ueno Guoren Deng Rajvir Dahiya |
| author_facet | Soichiro Yamamura Sharanjot Saini Shahana Majid Hiroshi Hirata Koji Ueno Guoren Deng Rajvir Dahiya |
| author_sort | Soichiro Yamamura |
| collection | DOAJ |
| description | MicroRNA-34a (miR-34a), a potent mediator of tumor suppressor p53, has been reported to function as a tumor suppressor and miR-34a was found to be downregulated in prostate cancer tissues. We studied the functional effects of miR-34a on c-Myc transcriptional complexes in PC-3 prostate cancer cells. Transfection of miR-34a into PC-3 cells strongly inhibited in vitro cell proliferation, cell invasion and promoted apoptosis. Transfection of miR-34a into PC-3 cells also significantly inhibited in vivo xenograft tumor growth in nude mice. miR-34a downregulated expression of c-Myc oncogene by targeting its 3' UTR as shown by luciferase reporter assays. miR-34a was found to repress RhoA, a regulator of cell migration and invasion, by suppressing c-Myc-Skp2-Miz1 transcriptional complex that activates RhoA. Overexpression of c-Myc reversed miR-34a suppression of RhoA expression, suggesting that miR-34a inhibits invasion by suppressing RhoA through c-Myc. miR-34a was also found to repress c-Myc-pTEFB transcription elongation complex, indicating one of the mechanisms by which miR-34a has profound effects on cellular function. This is the first report to document that miR-34a suppresses assembly and function of the c-Myc-Skp2-Miz1 complex that activates RhoA and the c-Myc-pTEFB complex that elongates transcription of various genes, suggesting a novel role of miR-34a in the regulation of transcription by c-Myc complex. |
| first_indexed | 2024-12-22T19:19:15Z |
| format | Article |
| id | doaj.art-39c6cdbb0c01409f9d135a870f0867c2 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T19:19:15Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-39c6cdbb0c01409f9d135a870f0867c22022-12-21T18:15:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0171e2972210.1371/journal.pone.0029722MicroRNA-34a modulates c-Myc transcriptional complexes to suppress malignancy in human prostate cancer cells.Soichiro YamamuraSharanjot SainiShahana MajidHiroshi HirataKoji UenoGuoren DengRajvir DahiyaMicroRNA-34a (miR-34a), a potent mediator of tumor suppressor p53, has been reported to function as a tumor suppressor and miR-34a was found to be downregulated in prostate cancer tissues. We studied the functional effects of miR-34a on c-Myc transcriptional complexes in PC-3 prostate cancer cells. Transfection of miR-34a into PC-3 cells strongly inhibited in vitro cell proliferation, cell invasion and promoted apoptosis. Transfection of miR-34a into PC-3 cells also significantly inhibited in vivo xenograft tumor growth in nude mice. miR-34a downregulated expression of c-Myc oncogene by targeting its 3' UTR as shown by luciferase reporter assays. miR-34a was found to repress RhoA, a regulator of cell migration and invasion, by suppressing c-Myc-Skp2-Miz1 transcriptional complex that activates RhoA. Overexpression of c-Myc reversed miR-34a suppression of RhoA expression, suggesting that miR-34a inhibits invasion by suppressing RhoA through c-Myc. miR-34a was also found to repress c-Myc-pTEFB transcription elongation complex, indicating one of the mechanisms by which miR-34a has profound effects on cellular function. This is the first report to document that miR-34a suppresses assembly and function of the c-Myc-Skp2-Miz1 complex that activates RhoA and the c-Myc-pTEFB complex that elongates transcription of various genes, suggesting a novel role of miR-34a in the regulation of transcription by c-Myc complex.http://europepmc.org/articles/PMC3250472?pdf=render |
| spellingShingle | Soichiro Yamamura Sharanjot Saini Shahana Majid Hiroshi Hirata Koji Ueno Guoren Deng Rajvir Dahiya MicroRNA-34a modulates c-Myc transcriptional complexes to suppress malignancy in human prostate cancer cells. PLoS ONE |
| title | MicroRNA-34a modulates c-Myc transcriptional complexes to suppress malignancy in human prostate cancer cells. |
| title_full | MicroRNA-34a modulates c-Myc transcriptional complexes to suppress malignancy in human prostate cancer cells. |
| title_fullStr | MicroRNA-34a modulates c-Myc transcriptional complexes to suppress malignancy in human prostate cancer cells. |
| title_full_unstemmed | MicroRNA-34a modulates c-Myc transcriptional complexes to suppress malignancy in human prostate cancer cells. |
| title_short | MicroRNA-34a modulates c-Myc transcriptional complexes to suppress malignancy in human prostate cancer cells. |
| title_sort | microrna 34a modulates c myc transcriptional complexes to suppress malignancy in human prostate cancer cells |
| url | http://europepmc.org/articles/PMC3250472?pdf=render |
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