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Cancer Cell. 2014 Aug 11;26(2):262-72. doi: 10.1016/j.ccr.2014.06.014.

MYC through miR-17-92 suppresses specific target genes to maintain survival, autonomous proliferation, and a neoplastic state.

Author information

1
Division of Oncology, Department of Medicine and Pathology, Stanford University, Stanford, CA 94305, USA.
2
Department of Computer Science, Stanford University, Stanford, CA 94305, USA.
3
Division of Oncology, Department of Medicine and Pathology, Stanford University, Stanford, CA 94305, USA. Electronic address: dfelsher@stanford.edu.

Abstract

The MYC oncogene regulates gene expression through multiple mechanisms, and its overexpression culminates in tumorigenesis. MYC inactivation reverses turmorigenesis through the loss of distinguishing features of cancer, including autonomous proliferation and survival. Here we report that MYC via miR-17-92 maintains a neoplastic state through the suppression of chromatin regulatory genes Sin3b, Hbp1, Suv420h1, and Btg1, as well as the apoptosis regulator Bim. The enforced expression of miR-17-92 prevents MYC suppression from inducing proliferative arrest, senescence, and apoptosis and abrogates sustained tumor regression. Knockdown of the five miR-17-92 target genes blocks senescence and apoptosis while it modestly delays proliferative arrest, thus partially recapitulating miR-17-92 function. We conclude that MYC, via miR-17-92, maintains a neoplastic state by suppressing specific target genes.

PMID:
25117713
PMCID:
PMC4191901
DOI:
10.1016/j.ccr.2014.06.014
[Indexed for MEDLINE]
Free PMC Article
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