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 Qin; Jindan Yu; Christopher A. Maher; Sooryanarayana Varambally; Arul M. Chinnaiyan

doi:10.1016/j.ccr.2011.06.016

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article

157 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 language	English (US)
Pages (from-to)	187-199
Number of pages	13
Journal	Cancer Cell
Volume	20
Issue number	2
DOIs	https://doi.org/10.1016/j.ccr.2011.06.016
Publication status	Published - Aug 16 2011

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ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

Cite this

Cao, Q., Mani, R. S., Ateeq, B., Dhanasekaran, S. M., Asangani, I. A., Prensner, J. R., ... 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

Cao, Qi ; Mani, Ram Shankar ; Ateeq, Bushra ; Dhanasekaran, Saravana M. ; Asangani, Irfan A. ; Prensner, John R. ; Kim, Jung H. ; Brenner, J. Chad ; Jing, Xiaojun ; Cao, Xuhong ; Wang, Rui ; Li, Yong ; Dahiya, Arun ; Wang, Lei ; Pandhi, Mithil ; Lonigro, Robert J. ; Wu, Yi Mi ; Tomlins, Scott A. ; Palanisamy, Nallasivam ; Qin, Zhaohui ; Yu, Jindan ; Maher, Christopher A. ; Varambally, Sooryanarayana ; Chinnaiyan, Arul M. / Coordinated Regulation of Polycomb Group Complexes through microRNAs in Cancer. In: Cancer Cell. 2011 ; Vol. 20, No. 2. pp. 187-199.

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title = "Coordinated Regulation of Polycomb Group Complexes through microRNAs in Cancer",

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.",

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

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Cao, Q, Mani, RS, Ateeq, B, Dhanasekaran, SM, Asangani, IA, Prensner, JR, Kim, JH, Brenner, JC, Jing, X, Cao, X, Wang, R, Li, Y, Dahiya, A, Wang, L, Pandhi, M, Lonigro, RJ, Wu, YM, Tomlins, SA, Palanisamy, N, Qin, Z, Yu, J, Maher, CA, Varambally, S & Chinnaiyan, AM 2011, 'Coordinated Regulation of Polycomb Group Complexes through microRNAs in Cancer', Cancer Cell, vol. 20, no. 2, pp. 187-199. https://doi.org/10.1016/j.ccr.2011.06.016

Coordinated Regulation of Polycomb Group Complexes through microRNAs in Cancer. / Cao, Qi; Mani, Ram Shankar; Ateeq, Bushra; Dhanasekaran, Saravana M.; Asangani, Irfan A.; Prensner, John R.; Kim, Jung H.; Brenner, J. Chad; Jing, Xiaojun; Cao, Xuhong; Wang, Rui; Li, Yong; Dahiya, Arun; Wang, Lei; Pandhi, Mithil; Lonigro, Robert J.; Wu, Yi Mi; Tomlins, Scott A.; Palanisamy, Nallasivam; Qin, Zhaohui; Yu, Jindan; Maher, Christopher A.; Varambally, Sooryanarayana; Chinnaiyan, Arul M.

In: Cancer Cell, Vol. 20, No. 2, 16.08.2011, p. 187-199.

Research output: Contribution to journal › Article

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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.

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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10.1016/j.ccr.2011.06.016