Widespread microRNA repression by Myc contributes to tumorigenesis

Tsung Cheng Chang, Duonan Yu, Yun Sil Lee, Erik A. Wentzel, Dan E. Arking, Kristin M. West, Chi V. Dang, Andrei Thomas-Tikhonenko, Joshua T. Mendell

Research output: Contribution to journalArticle

982 Scopus citations

Abstract

The c-Myc oncogenic transcription factor (Myc) is pathologically activated in many human malignancies. Myc is known to directly upregulate a pro-tumorigenic group of microRNAs (miRNAs) known as the miR-17-92 cluster. Through the analysis of human and mouse models of B cell lymphoma, we show here that Myc regulates a much broader set of miRNAs than previously anticipated. Unexpectedly, the predominant consequence of activation of Myc is widespread repression of miRNA expression. Chromatin immunoprecipitation reveals that much of this repression is likely to be a direct result of Myc binding to miRNA promoters. We further show that enforced expression of repressed miRNAs diminishes the tumorigenic potential of lymphoma cells. These results demonstrate that extensive reprogramming of the miRNA transcriptome by Myc contributes to tumorigenesis.

Original languageEnglish (US)
Pages (from-to)43-50
Number of pages8
JournalNature genetics
Volume40
Issue number1
DOIs
StatePublished - Jan 1 2008

ASJC Scopus subject areas

  • Genetics

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    Chang, T. C., Yu, D., Lee, Y. S., Wentzel, E. A., Arking, D. E., West, K. M., Dang, C. V., Thomas-Tikhonenko, A., & Mendell, J. T. (2008). Widespread microRNA repression by Myc contributes to tumorigenesis. Nature genetics, 40(1), 43-50. https://doi.org/10.1038/ng.2007.30