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Regulation and Role of EZH2 in Cancer
Hirohito Yamaguchi,Mien-Chie Hung 대한암학회 2014 Cancer Research and Treatment Vol.46 No.3
Polycomb repressive complex 2 (PRC2) is the epigenetic regulator that induces histone H3lysine 27 methylation (H3K27me3) and silences specific gene transcription. Enhancer ofzeste homolog 2 (EZH2) is an enzymatic subunit of PRC2, and evidence shows that EZH2plays an essential role in cancer initiation, development, progression, metastasis, and drugresistance. EZH2 expression is indeed regulated by various oncogenic transcription factors,tumor suppressor miRNAs, and cancer-associated non-coding RNA. EZH2 activity is alsocontrolled by post-translational modifications, which are deregulated in cancer. The canonicalrole of EZH2 is gene silencing through H3K27me3, but accumulating evidence showsthat EZH2 methlyates substrates other than histone and has methylase-independentfunctions. These non-canonical functions of EZH2 are shown to play a role in cancerprogression. In this review, we summarize current information on the regulation and rolesof EZH2 in cancer. We also discuss various therapeutic approaches to targeting EZH2.