Multifaceted role of the polycomb-group gene EZH2 in hematological malignancies
Multifaceted role of the polycomb-group gene EZH2 in hematological malignancies
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DOI：
10.1007/s12185-016-2124-x
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发表时间：
2017-01-01
影响因子：
2.1
通讯作者：
Iwama, Atsushi
中科院分区：
文献类型：
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作者：
Sashida, Goro;Iwama, Atsushi
多梳抑制复合体(PRC)是正常组织动态平衡和肿瘤发生的重要调节因子。EZH2是一种组蛋白H3K27甲基转移酶，是PrC2的一个酶亚基，参与基因沉默的调节。EZH2的过度表达首先在前列腺癌和乳腺癌中被发现，并与不良的临床结果有关。随后，在包括血液系统恶性肿瘤在内的各种肿瘤中发现了EZH2的功能缺失突变，这表明EZH2可能是癌基因，也可能是肿瘤抑制基因，具体取决于癌症类型。对EZH2多方面功能的分子机制进行了广泛的分析。然而，由于EZH2异常与其他多种表观遗传事件在功能上是以上下文相关的方式整合在一起的，EZH2异常影响血液系统恶性肿瘤发病机制的确切方式仍有待阐明。从这个角度，我们描述了EZH2在血液系统恶性肿瘤中致病作用的最新研究结果，这些发现可能为EZH2调控异常的癌症的治疗和针对表观遗传调节因子的新疗法的开发提供见解。
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.