Liu Chengyin, Tang Han, Hu Nana, Li Tianbao
Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Georgetown University, Washington, DC, USA.
BioChain (Beijing) Science & Technology Inc., Beijing, People's Republic of China.
Cancer Cell Int. 2023 Oct 16;23(1):242. doi: 10.1186/s12935-023-03074-7.
Epigenetic modifications have long been recognized as an essential level in transcriptional regulation linking behavior and environmental conditions or stimuli with biological processes and disease development. Among them, methylation is the most abundant of these reversible epigenetic marks, predominantly occurring on DNA, RNA, and histones. Methylation modification is intimately involved in regulating gene transcription and cell differentiation, while aberrant methylation status has been linked with cancer development in several malignancies. Early detection and precise restoration of dysregulated methylation form the basis for several epigenetics-based therapeutic strategies. In this review, we summarize the current basic understanding of the regulation and mechanisms responsible for methylation modification and cover several cutting-edge research techniques for detecting methylation across the genome and transcriptome. We then explore recent advances in clinical diagnostic applications of methylation markers of various cancers and address the current state and future prospects of methylation modifications in therapies for different diseases, especially comparing pharmacological methylase/demethylase inhibitors with the CRISPRoff/on methylation editing systems. This review thus provides a resource for understanding the emerging role of epigenetic methylation in cancer, the use of methylation-based biomarkers in cancer detection, and novel methylation-targeted drugs.
表观遗传修饰长期以来一直被认为是转录调控中的一个重要层面，它将行为、环境条件或刺激与生物过程及疾病发展联系起来。其中，甲基化是这些可逆表观遗传标记中最为常见的，主要发生在DNA、RNA和组蛋白上。甲基化修饰密切参与基因转录和细胞分化的调控，而异常的甲基化状态在多种恶性肿瘤的发生发展中都有联系。早期检测和精确恢复失调的甲基化是几种基于表观遗传学的治疗策略的基础。在这篇综述中，我们总结了目前对甲基化修饰调控及其机制的基本认识，并介绍了几种用于检测全基因组和转录组甲基化的前沿研究技术。然后，我们探讨了各种癌症甲基化标志物在临床诊断应用中的最新进展，并阐述了甲基化修饰在不同疾病治疗中的现状和未来前景，特别是将药理学甲基化酶/去甲基化酶抑制剂与CRISPRoff/on甲基化编辑系统进行比较。因此，这篇综述为理解表观遗传甲基化在癌症中的新兴作用、基于甲基化的生物标志物在癌症检测中的应用以及新型甲基化靶向药物提供了参考资源。
