这篇综述的讨论集中在EZH2和启动之间的重要关系,programming,转移,新陈代谢,耐药性,和癌症的免疫调节。多梳组(PcG)蛋白,包含两个主要的Polycomb阻遏复合物(PRC1和PRC2),已被分类。PRC2主要由四个亚基组成,即EZH2,EED,SUZ12和RbAp46/48。作为PRC2复合物中的关键催化组分,EZH2在控制广泛的生物过程中起着关键作用。已经在多种肿瘤中检测到EZH2的过表达/突变。已经确定了几种EZH调节机制,包括通过miRNA调节EZH2mRNA,LncRNAs,通过DNA结合蛋白获得DNA,翻译后修饰,和转录调控。EZH2信号传导引发癌症进展并可能干预抗肿瘤免疫;因此它作为癌症治疗中的有效治疗靶标引起了关注。基于核酸的数字疗法已用于EZH2的修饰。除了基因治疗方法,药物化合物可用于靶向EZH2信号通路治疗癌症。EZH2相关的肿瘤细胞和免疫细胞增强了多种人类恶性肿瘤中免疫应答的作用。表观遗传修饰剂的组合,如抗EZH2化合物与免疫治疗,即使在免疫抑制肿瘤的情况下,也可能是有效的。Summary,了解EZH2抑制剂耐药的潜在机制可能有助于开发预防或治疗患者复发的新药.
The discussion in this review centers around the significant relationships between
EZH2 and the initiation, progression, metastasis, metabolism, drug resistance, and immune regulation of cancer. Polycomb group (PcG) proteins, which encompass two primary Polycomb repressor complexes (PRC1 and PRC2), have been categorized. PRC2 consists mainly of four subunits, namely
EZH2, EED, SUZ12, and RbAp46/48. As the crucial catalytic component within the PRC2 complex,
EZH2 plays a pivotal role in controlling a wide range of biological processes. Overexpression/mutations of
EZH2 have been detected in a wide variety of tumors. Several mechanisms of EZH regulation have been identified, including regulation EZH2 mRNA by miRNAs, LncRNAs, accessibility to DNA via DNA-binding proteins, post-translational modifications, and transcriptional regulation. EZH2 signaling triggers cancer progression and may intervene with anti-tumor immunity; therefore it has charmed attention as an effective therapeutic target in cancer therapy. Numerouss nucleic acid-based therapies have been used in the modification of
EZH2. In addition to gene therapy approaches, pharmaceutical compounds can be used to target the EZH2 signaling pathway in the treatment of cancer. EZH2-associated tumor cells and immune cells enhance the effects of the immune response in a variety of human malignancies. The combination of epigenetic modifying agents, such as anti-EZH2 compounds with immunotherapy, could potentially be efficacious even in the context of immunosuppressive tumors. Summary, understanding the mechanisms underlying resistance to EZH2 inhibitors may facilitate the development of novel drugs to prevent or treat relapse in treated patients.