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EZH2 在骨髓间充质干细胞与免疫-癌症相互作用中的作用。

Role of EZH2 in bone marrow mesenchymal stem cells and immune-cancer interactions.

机构信息

Department of Hematology, Tianjin Medical University General Hospital, 154 Anshan Street, Heping District, Tianjin, 300052, PR China.

出版信息

Crit Rev Oncol Hematol. 2022 Jan;169:103547. doi: 10.1016/j.critrevonc.2021.103547. Epub 2021 Nov 26.

Abstract

In recent years, methylation modification has been determined to be vital for the biological regulation of normal cells, tumor cells, and tumor microenvironment immune cells. Enhancer of zeste homology 2 (EZH2), a component of the Polycomb Repressive Complex 2 (PRC2), catalyzes the trimethylation of the downstream gene in the tri-methylates histone three lysine 27 (H3K27me3) position, which causes chromatin pyknosis, and thus, silences the expression of related genes. In this paper, we reviewed the role of EZH2 in regulating bone marrow mesenchymal stem cell differentiation and the immune cell function in tumor microenvironment, summarized all types of existing EZH2 inhibitors and the main clinical trials, and proposed relevant ideas for potential clinical applications.

摘要

近年来,甲基化修饰被确定对正常细胞、肿瘤细胞和肿瘤微环境免疫细胞的生物学调控至关重要。EZH2(增强子结合锌指蛋白 2)是 Polycomb 抑制复合物 2(PRC2)的一个组成部分,它催化下游基因在三甲基化组蛋白 3 赖氨酸 27(H3K27me3)位置的三甲基化,导致染色质固缩,从而使相关基因沉默。本文综述了 EZH2 在调节骨髓间充质干细胞分化和肿瘤微环境中免疫细胞功能中的作用,总结了所有类型现有的 EZH2 抑制剂及其主要临床试验,并对潜在的临床应用提出了相关的想法。

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