Multifaceted role of the polycomb-group gene EZH2 in hematological malignancies.
Polycomb repressive complex (PRC) is a critical regulator of normal tissue homeostasis as well as tumorigenesis. EZH2, an enzymatic subunit of PRC2, is a histone H3K27 methyltransferase that functions in the regulation of gene silencing. EZH2 overexpression was first identified in prostate and breast cancers and is associated with poor clinical outcome. Subsequently, gain- and loss-of-function mutations of EZH2 have been identified in various tumors, including hematological malignancies, implicating EZH2 as either an oncogene or a tumor suppressor gene, depending on the cancer type. Molecular mechanisms underlying the multifaceted function of EZH2 have been analyzed extensively. However, because EZH2 dysregulation is functionally integrated with multiple other epigenetic events in a context-dependent manner, the precise manner in which EZH2 dysregulation impacts the pathogenesis of hematological malignancies remains to be clarified. In this perspective, we describe recent findings in pathogenic role of EZH2 in hematological malignancies, which may provide insights into the treatment of with cancers with EZH2 dysregulation and the development of novel therapies targeting epigenetic regulators.
International Research Center for Medical Sciences, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan. sashidag@kumamoto-u.ac.jp.
Goro
G
Sashida
Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
Atsushi
A
Iwama
D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics*; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000473:pathology; D006410:Hematopoiesis; D006801:Humans; D009154:Mutation
C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein
EZH1; EZH2; Epigenetic switch; H3K27me3; Polycomb-group genes