MYC through miR-17-92 Suppresses Specific Target Genes to Maintain Survival, Autonomous Proliferation, and a Neoplastic State
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AbstractThe 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.
CitationLi Y, Choi PS, Casey SC, Dill DL, Felsher DW (2014) MYC through miR-17-92 Suppresses Specific Target Genes to Maintain Survival, Autonomous Proliferation, and a Neoplastic State. Cancer Cell 26: 262–272. Available: http://dx.doi.org/10.1016/j.ccr.2014.06.014.
SponsorsWe thank members of the Felsher Laboratory for generously providing their suggestions and thoughtful discussions. This work was supported by the NIH R01CA170378 (D.W.F.), U54CA149145 (D.W.F. and D.L.D.), U54CA143907 (D.W.F. and Y.L.), and 1F32CA177139 and 5T32A107290 (S.C.C.) grants; the Leukemia and Lymphoma Society Translational Research grant R6223-07 (D.W.F.); and a King Abdullah University of Science and Technology research grant (D.L.D.).
PubMed Central IDPMC4191901
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