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癌症治疗与进展中的表观遗传调控因子

Epigenetic regulators in cancer therapy and progression.

作者信息

Marei Hany E

机构信息

Department of Cytology and Histology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.

出版信息

NPJ Precis Oncol. 2025 Jun 28;9(1):206. doi: 10.1038/s41698-025-01003-7.

Abstract

Heritable gene activity variations that do not alter the underlying DNA sequence are known as epigenetic modifications. Mutations that disrupt genome structure and function are key drivers of oncogenesis. In addition to genetic mutations that cause direct disruptions in the DNA sequence, epigenetic changes can affect gene expression, which helps the development of cancerous traits. Changes in DNA methylation and histone mark patterns are the main drivers of these epigenetic modifications, as they encourage the growth and spread of tumors. In this review, we explore the substantial implications of epigenetic control on tumor genesis, metastatic behaviour, metabolic pathways, and the tumor microenvironment, delving into the intricacies of this intricate regulation. We pay special attention to the dysregulation at every stage of epigenetic modulation, which includes, but is not limited to, abnormalities in the enzymes that modify histones and methylate DNA, subunit loss or fusions in chromatin remodeling complexes, and disruptions in higher-order chromatin structure. We also highlight the development of inhibitors of medications targeted at epigenetic enzymes and summarize the abnormal roles of enzymes in DNA methylation, histone acetylation, and histone methylation during tumour progression.

摘要

不改变潜在DNA序列的可遗传基因活性变化被称为表观遗传修饰。破坏基因组结构和功能的突变是肿瘤发生的关键驱动因素。除了导致DNA序列直接破坏的基因突变外,表观遗传变化会影响基因表达,这有助于癌性特征的发展。DNA甲基化和组蛋白标记模式的变化是这些表观遗传修饰的主要驱动因素,因为它们促进肿瘤的生长和扩散。在本综述中,我们探讨了表观遗传控制对肿瘤发生、转移行为、代谢途径和肿瘤微环境的重大影响,深入研究这种复杂调控的复杂性。我们特别关注表观遗传调控每个阶段的失调,这包括但不限于修饰组蛋白和使DNA甲基化的酶的异常、染色质重塑复合物中的亚基缺失或融合,以及高阶染色质结构的破坏。我们还强调了针对表观遗传酶的药物抑制剂的开发,并总结了肿瘤进展过程中酶在DNA甲基化、组蛋白乙酰化和组蛋白甲基化中的异常作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fef/12206235/41bc449d24d2/41698_2025_1003_Fig1_HTML.jpg

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