Author/Authors :
Cao، نويسنده , , Qi and Mani، نويسنده , , Ram-Shankar and Ateeq، نويسنده , , Bushra and Dhanasekaran، نويسنده , , Saravana M. and Asangani، نويسنده , , Irfan A. and Prensner، نويسنده , , John R. and Kim، نويسنده , , Jung H. and Brenner، نويسنده , , J. Chad and Jing، نويسنده , , Xiaojun and Cao، نويسنده , , Xuhong and Wang، نويسنده , , Rui and Li، نويسنده , , Yong and Dahiya، نويسنده , , Arun and Wang، نويسنده , , Lei and Pandhi، نويسنده , , Mithil and Lonigro، نويسنده , , Robert J. and Wu، نويسنده , , Yi-Mi and Tomlins، نويسنده , , Scott A. and Palanisamy، نويسنده , , Nallasivam and Qin، نويسنده , , Zhaohui and Yu، نويسنده , , Jindan and Maher، نويسنده , , Christopher A. and Varambally، نويسنده , , Sooryanarayana and Chinnaiyan، نويسنده , , Arul M.، نويسنده ,
Abstract :
Summary
mb Repressive Complexes (PRC1 and PRC2)-mediated epigenetic regulation is critical for maintaining cellular homeostasis. Members of Polycomb Group (PcG) proteins including EZH2, a PRC2 component, are upregulated in various cancer types, implicating their role in tumorigenesis. Here, we have identified several microRNAs (miRNAs) that are repressed by EZH2. These miRNAs, in turn, regulate the expression of PRC1 proteins BMI1 and RING2. We found that ectopic overexpression of EZH2-regulated miRNAs attenuated cancer cell growth and invasiveness, and abrogated cancer stem cell properties. Importantly, expression analysis revealed an inverse correlation between miRNA and PRC protein levels in cell culture and prostate cancer tissues. Taken together, our data have uncovered a coordinate regulation of PRC1 and PRC2 activities that is mediated by miRNAs.
