Article abstract


Nature Genetics 40, 43 - 50 (2008)
Published online: 9 December 2007 | doi:10.1038/ng.2007.30

Widespread microRNA repression by Myc contributes to tumorigenesis

Tsung-Cheng Chang1,7, Duonan Yu2,7, Yun-Sil Lee1, Erik A Wentzel1, Dan E Arking1,3, Kristin M West1, Chi V Dang3,4, Andrei Thomas-Tikhonenko2 & Joshua T Mendell1,5,6


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.

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  1. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
  2. Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
  3. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
  4. The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
  5. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
  6. Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
  7. These authors contributed equally to this work.

Correspondence to: Joshua T Mendell1,5,6 e-mail: jmendell@jhmi.edu

Correspondence to: Andrei Thomas-Tikhonenko2 e-mail: andreit@mail.vet.upenn.edu



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