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The Role of microRNA miR-101 in Prostate Cancer Progression
Annual summary rept. 1 Sep 2010-31 Aug 2012
MICHIGAN UNIV ANN ARBOR
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Polycomb group PcG proteins are chromatin-modifying complexes that regulate epigenetic silencing and play an important role in determining cell fate. PcG proteins form two major complexes, Polycomb repressive Complex 1 PRC1 and Polycomb repressive Complex 2 PRC2. PRC2 methylates histone H3 on lysin 27 H3K27 creating a chromatin mark which stimulates PRC1 to enact gene silencing at target genes. Employing in vitro and in vivo cancer models, combined with human tumor studies, we demonstrate that PRC2 and PRC1 coordinate their function through regulation of specific microRNAs including miR-203, miR-181a, b and miR-200b, c. Increased PRC2 activity in cancer leads to repression of these microRNAs, which in turn leads to increased expression of PRC1 componenets. Thus, we propose that key microRNAs link PRC2 to PRC1 forming an integrat regulatory axis of the epigenetic silencing machinery.
APPROVED FOR PUBLIC RELEASE