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PMID: 22235332 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

MicroRNA-34a modulates c-Myc transcriptional complexes to suppress malignancy in human prostate cancer cells.

PloS one ·Vol. 7 ·No. 1 ·2012-00-00 ·Pages e29722

Yamamura S, Saini S, Majid S, Hirata H, Ueno K, Deng G, Dahiya R

Abstract

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.

MeSH Terms
Animals Cell Line, Tumor Cell Movement/genetics Cell Proliferation Down-Regulation Female Humans Male Mice MicroRNAs/genetics,metabolism Neoplasm Invasiveness Positive Transcriptional Elongation Factor B/metabolism Prostatic Neoplasms/pathology Proto-Oncogene Proteins c-met/metabolism Proto-Oncogene Proteins c-myc/metabolism Transcription, Genetic/genetics rhoA GTP-Binding Protein/metabolism
Chemicals
MIRN34 microRNA, human MicroRNAs Proto-Oncogene Proteins c-myc Proto-Oncogene Proteins c-met Positive Transcriptional Elongation Factor B rhoA GTP-Binding Protein
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Yamamura Soichiro
Department of Urology, San Francisco Veterans Affairs Medical Center and University of California San Francisco, San Francisco, California, United States of America.
Saini Sharanjot
Majid Shahana
Hirata Hiroshi
Ueno Koji
Deng Guoren
Dahiya Rajvir
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0029722
Published
2012-00-00
Epub
2012-00-03
Pages
e29722
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3250472
Subset
IM
Grants
NCI NIH HHS · R01 CA138642 · United States
NIDDK NIH HHS · T32 DK007790 · United States
NCI NIH HHS · R01CA138642 · United States
NIDDK NIH HHS · T32DK007790 · United States
External Links
PubMed source DOI: 10.1371/journal.pone.0029722 PMC Full Text View journal details
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