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

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 - Feb 8 2012
Externally publishedYes

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MicroRNAs
Renal Cell Carcinoma
Positive Transcriptional Elongation Factor B
3' Untranslated Regions
Luciferases
Oncogenes

ASJC Scopus subject areas

  • Cancer Research

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Microrna-34a suppresses malignant transformation by targeting c-myc transcriptional complexes in human renal cell carcinoma. / Yamamura, Soichiro; Saini, Sharanjot; Majid, Shahana; Hirata, Hiroshi; Ueno, Koji; Chang, Inik; Tanaka, Yuichiro; Gupta, Ashish; Dahiya, Rajvir.

In: Carcinogenesis, Vol. 33, No. 2, 08.02.2012, p. 294-300.

Research output: Contribution to journalArticle

Yamamura, S, Saini, S, Majid, S, Hirata, H, Ueno, K, Chang, I, Tanaka, Y, Gupta, A & Dahiya, R 2012, 'Microrna-34a suppresses malignant transformation by targeting c-myc transcriptional complexes in human renal cell carcinoma', Carcinogenesis, vol. 33, no. 2, pp. 294-300. https://doi.org/10.1093/carcin/bgr286
Yamamura, Soichiro ; Saini, Sharanjot ; Majid, Shahana ; Hirata, Hiroshi ; Ueno, Koji ; Chang, Inik ; Tanaka, Yuichiro ; Gupta, Ashish ; Dahiya, Rajvir. / Microrna-34a suppresses malignant transformation by targeting c-myc transcriptional complexes in human renal cell carcinoma. In: Carcinogenesis. 2012 ; Vol. 33, No. 2. pp. 294-300.
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