Myc-induced microRNAs integrate Myc-mediated cell proliferation and cell fate

Abstract

The Myc pathway, often deregulated in cancer, is critical in determining cell fate by coordinating a gene expression program that links the control of cell proliferation with cell fate decisions. As such, precise control of the Myc pathway activity must be achieved to ensure faithful execution of appropriate cellular response and to prevent progressing toward a malignant state. With recent highlighted roles of microRNAs (miRNA) as critical components of gene control, we sought to evaluate the extent to which miRNAs may contribute in the execution of Myc function. Combined analysis of mRNA and miRNA expression profiles reveals an integration whereby the Myc-mediated induction of miRNAs leads to the repression of various mRNAs encoding tumor suppressors that block cell proliferation including p21, p27, and Rb. In addition, the proapoptotic PTEN tumor suppressor gene is also repressed by Myc-induced miRNAs, suggesting that Myc-induced miRNAs contribute to the precise control of a transcriptional program that coordinates the balance of cell proliferation and cell death. ©2010 AACR.