We investigated the functional effects of microRNA-34a (miR-34a) on c-Myc transcriptional complexes in renal cell carcinoma.
miR-34a down-regulated expression of multiple oncogenes including c-Myc by targeting its 3' untranslated region, which was revealed by luciferase reporter assays. miR-34a was also found to repress RhoA expression by suppressing the c-Myc-Skp2-Miz1 transcriptional complex that activates RhoA. Overexpression of c-Myc reversed miR-34a suppression of RhoA expression and inhibition of cell invasion, suggesting that miR-34a inhibits invasion by suppressing RhoA through c-Myc. miR-34a was also found to repress the c-Myc-P-TEFb transcription elongation complex, indicating one of the mechanisms by which miR-34a has profound effects on cellular functions. Our results demonstrate that miR-34a suppresses assembly and function of the c-Myc complex that activates or elongates transcription, indicating a novel role of miR-34a in the regulation of transcription by c-Myc.
Written by:
Yamamura S, Saini S, Majid S, Hirata H, Ueno K, Chang I, Tanaka Y, Gupta A, Dahiya R. Are you the author?
Department of Urology, San Francisco Veterans Affairs Medical Center and University of California, San Francisco, CA 94121, USA.
Reference: Carcinogenesis. 2012 Feb;33(2):294-300. Epub 2011 Dec 9.
PubMed Abstract
PMID: 22159222
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