Microrna-34a suppresses malignant transformation by targeting c-myc transcriptional complexes in human renal cell carcinoma

Soichiro Yamamura, Sharanjot Saini, Shahana Majid, Hiroshi Hirata, Koji Ueno, Inik Chang, Yuichiro Tanaka, Ashish Gupta, Rajvir Dahiya

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)294-300
Number of pages7
JournalCarcinogenesis
Volume33
Issue number2
DOIs
StatePublished - 2012

ASJC Scopus subject areas

  • Cancer Research

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