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.
authors.affiliation: Michigan Center for Translational Pathology, Ann Arbor, MI 48109, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Cao
authors.forename: Ram-Shankar
authors.initials: RS
authors.lastname: Mani
authors.forename: Bushra
authors.initials: B
authors.lastname: Ateeq
authors.forename: Saravana M
authors.initials: SM
authors.lastname: Dhanasekaran
authors.forename: Irfan A
authors.initials: IA
authors.lastname: Asangani
authors.forename: John R
authors.initials: JR
authors.lastname: Prensner
authors.forename: Jung H
authors.initials: JH
authors.lastname: Kim
authors.forename: J Chad
authors.initials: JC
authors.lastname: Brenner
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Jing
authors.forename: Xuhong
authors.initials: X
authors.lastname: Cao
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Arun
authors.initials: A
authors.lastname: Dahiya
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Mithil
authors.initials: M
authors.lastname: Pandhi
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lonigro
authors.forename: Yi-Mi
authors.initials: YM
authors.lastname: Wu
authors.forename: Scott A
authors.initials: SA
authors.lastname: Tomlins
authors.forename: Nallasivam
authors.initials: N
authors.lastname: Palanisamy
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Qin
authors.forename: Jindan
authors.initials: J
authors.lastname: Yu
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Maher
authors.forename: Sooryanarayana
authors.initials: S
authors.lastname: Varambally
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
mesh_terms: D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins / Q000502:physiology*
chemical_list: D035683:MicroRNAs; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins