TY - JOUR
T1 - Coordinated Regulation of Polycomb Group Complexes through microRNAs in Cancer
AU - Cao, Qi
AU - Mani, Ram Shankar
AU - Ateeq, Bushra
AU - Dhanasekaran, Saravana M.
AU - Asangani, Irfan A.
AU - Prensner, John R.
AU - Kim, Jung H.
AU - Brenner, J. Chad
AU - Jing, Xiaojun
AU - Cao, Xuhong
AU - Wang, Rui
AU - Li, Yong
AU - Dahiya, Arun
AU - Wang, Lei
AU - Pandhi, Mithil
AU - Lonigro, Robert J.
AU - Wu, Yi Mi
AU - Tomlins, Scott A.
AU - Palanisamy, Nallasivam
AU - Qin, Zhaohui
AU - Yu, Jindan
AU - Maher, Christopher A.
AU - Varambally, Sooryanarayana
AU - Chinnaiyan, Arul M.
N1 - Funding Information:
We thank Xia Jiang, Javed Siddiqui, Wei Yan, Bo Han, Khalid Suleman, Rohit Mehra, Rupal Shastri, and Joy E. Tsai for technical assistance, Victor E. Marquez for providing DZNep, Michigan Center for hES Cell Research for H7 RNA and qPCR, the University of Michigan Vector Core for generating adenovirus and lentivirus, Kenneth J. Pienta, Xiaosong Wang, and Shanker Kalyana-Sundaram for discussions, and Jyoti Athanikar and Karen Giles for critically reading the manuscript and submission documents. This work is supported in part by the Early Detection Research Network UO1 CA111275, Prostate SPORE P50CA69568 and P50CA090386, and National Institutes of Health (R01CA132874, R01CA157845). A.M.C. is supported by the Doris Duke Charitable Foundation Clinical Scientist Award, Burroughs Welcome Foundation Award in Clinical Translational Research, the Prostate Cancer Foundation (PCF) and the Howard Hughes Medical Institute. A.M.C. is an American Cancer Society Research Professor. Q.C., J.R.P., and J.C.B. are supported by U.S. Department of Defense (PC094725 to Q.C.; PC094290 to J.R.P.; BC083217 to J.C.B.); R.-S.M., S.A.T., and C.A.M. are supported by Young Investigator Awards from the PCF; B.A. is supported by the Genentech Foundation Postdoctoral Fellowship and Young Investigator Award from the Expedition Inspiration Fund for Breast Cancer Research. N.P. is supported by the University of Michigan Prostate Cancer SPORE Career Development award. Z.Q. is supported by National Institutes of Health (7R01HG005119-02). J.Y. is supported by U.S. Department of Defense (PC080665) and National Institutes of Health (5R00CA129565); S.V. is supported by National Institutes of Health (R01CA157845) and Prostate Cancer SPORE Career Development award. Q.C. and A.M.C. designed the experiments. Q.C., R.-S.M., B.A., S.M.D., I.A.A., J.R.P., J.H.K., J.C.B., X.J., X.C., R.W., Y.L., A.D., L.W., M.P., Y.-M.W., S.A.T., N.P., J.Y., and S.V. performed the experimental work. R.J.L., Z.Q., and C.A.M. performed statistical analysis on miRNA and gene expression data. Q.C. and A.M.C. wrote the paper. All authors discussed the results and commented on the manuscript.
PY - 2011/8/16
Y1 - 2011/8/16
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ccr.2011.06.016
DO - 10.1016/j.ccr.2011.06.016
M3 - Article
C2 - 21840484
AN - SCOPUS:80051590718
VL - 20
SP - 187
EP - 199
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 2
ER -