Multifaceted role of the polycomb-group gene EZH2 in hematological malignancies

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• 作者：Goro Sashida ; Atsushi Iwama
• 关键词：Polycomb ; group genes ; EZH2 ; EZH1 ; H3K27me3 ; Epigenetic switch
• 刊名：International Journal of Hematology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：105
• 期：1
• 页码：23-30
• 全文大小：882KB
• 刊物主题：Hematology; Oncology;
• 出版者：Springer Japan
• ISSN：1865-3774
• 卷排序：105

文摘

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.