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Widespread microRNA repression by Myc contributes to tumorigenesis.

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.

SUBMITTER: Chang TC

PROVIDER: S-EPMC2628762 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

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Widespread microRNA repression by Myc contributes to tumorigenesis.

Chang Tsung-Cheng TC Yu Duonan D Lee Yun-Sil YS Wentzel Erik A EA Arking Dan E DE West Kristin M KM Dang Chi V CV Thomas-Tikhonenko Andrei A Mendell Joshua T JT

Nature genetics 20071209 1

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 immunop ...[more]

PMID: 18066065

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