组蛋白甲基化修饰在子宫内膜癌中的研究进展

doi:10.12280/gjfckx.20220438

摘要/Abstract

摘要：

子宫内膜癌是一种子宫内膜上皮源性的恶性肿瘤。雌激素刺激、肥胖、糖尿病、高血压和未孕未产等因素是其发病的高危因素。近年研究发现，表观遗传修饰在子宫内膜癌中起重要作用。随着组蛋白甲基化修饰在子宫内膜癌中的研究逐渐深入，越来越多的研究发现组蛋白甲基化修饰作为基因转录的重要一环具有复杂的生物学行为。组蛋白甲基化相关的酶与癌症的发生密切相关，其可能通过调节启动子、增强子、外显子和重复序列等基因结构的组蛋白甲基化，使下游基因重编程，从而在子宫内膜癌的发生、发展及预后中发挥重要作用。未来有望通过靶向组蛋白甲基化相关的酶来调节基因的生物学行为，从而预防和治疗子宫内膜癌。

关键词: 组蛋白类, 甲基化, 表观基因组学, 组蛋白甲基转移酶类, 组蛋白脱甲基酶类, 子宫内膜肿瘤

Abstract:

Endometrial carcinoma is a malignant tumor of endometrial epithelium. Factors such as estrogen stimulation, obesity, diabetes, hypertension and non-pregnancy are high risk factors for its development. Recent studies have found that epigenetic modification also plays an important role in endometrial carcinoma. With the deepening of the research on histone methylation modification in endometrial carcinoma, more and more studies have found that histone methylation modification has complex biological behavior as an important part of gene transcription. Histone methylation-related enzymes are closely related to the occurrence of cancer. They may reprogram downstream genes by regulating histone methylation of promoters, enhancers, exons, repeats and other gene structures, thus playing an important role in the occurrence, development and prognosis of endometrial carcinoma. In the future, we may be able to regulate the biological behavior of genes by targeting histone methylation-related enzymes to better prevent and treat endometrial carcinoma.

Key words: Histones, Methylation, Epigenomics, Histone methyltransferases, Histone demethylases, Endometrial neoplasms

温馨, 王博, 马晓欣. 组蛋白甲基化修饰在子宫内膜癌中的研究进展[J]. 国际妇产科学杂志, 2023, 50(1): 1-5.

WEN Xin, WANG Bo, MA Xiao-xin. Research Progress of Histone Methylation Modification in Endometrial Carcinoma[J]. Journal of International Obstetrics and Gynecology, 2023, 50(1): 1-5.

图/表 2

图1 组蛋白甲基化流程和参与修饰的酶注：KMT 赖氨酸甲基转移酶，PRMT 组蛋白精氨酸甲基转移酶，KDM 赖氨酸去甲基化酶，LSD 赖氨酸特异性去甲基化酶。a~c为组蛋白甲基化；d~f为组蛋白去甲基化。LSD只参与d和e流程；KDM2~KDM7可以参与d~f的任一流程。

图2 组蛋白甲基化参与子宫内膜癌发生、发展的机制注：促进基因转录的甲基化组蛋白包括H3K27me1、H3K27me2、H3K4me2和H3K4me3；抑制基因转录的甲基化组蛋白包括H3K9me2、H3K9me3和H3K27me3。

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