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

Y Li, PS Choi, SC Casey, DL Dill, DW Felsher - Cancer cell, 2014 - cell.com
Y Li, PS Choi, SC Casey, DL Dill, DW Felsher
Cancer cell, 2014cell.com
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 …
Summary
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.
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