Coordinated Regulation of Polycomb Group Complexes through microRNAs in Cancer

Qi Cao, Ram Shankar Mani, Bushra Ateeq, Saravana M. Dhanasekaran, Irfan A. Asangani, John R. Prensner, Jung H. Kim, J. Chad Brenner, Xiaojun Jing, Xuhong Cao, Rui Wang, Yong Li, Arun Dahiya, Lei Wang, Mithil Pandhi, Robert J. Lonigro, Yi Mi Wu, Scott A. Tomlins, Nallasivam Palanisamy, Zhaohui QinJindan Yu, Christopher A. Maher, Sooryanarayana Varambally, Arul M. Chinnaiyan

Research output: Contribution to journalArticle

161 Scopus citations

Abstract

Polycomb 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.

Original languageEnglish (US)
Pages (from-to)187-199
Number of pages13
JournalCancer Cell
Volume20
Issue number2
DOIs
StatePublished - Aug 16 2011

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Cao, Q., Mani, R. S., Ateeq, B., Dhanasekaran, S. M., Asangani, I. A., Prensner, J. R., Kim, J. H., Brenner, J. C., Jing, X., Cao, X., Wang, R., Li, Y., Dahiya, A., Wang, L., Pandhi, M., Lonigro, R. J., Wu, Y. M., Tomlins, S. A., Palanisamy, N., ... Chinnaiyan, A. M. (2011). Coordinated Regulation of Polycomb Group Complexes through microRNAs in Cancer. Cancer Cell, 20(2), 187-199. https://doi.org/10.1016/j.ccr.2011.06.016