Zahoor Ambreen, Khazer Rafia, Mehraj Insha, Gani Ubaid, Fayaz Falah, Khanday Firdous A, Bhat Sahar Saleem
Division of Animal Biotechnology, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST-K, Srinagar, 190006, J&K, India.
Department of Biotechnology, University of Kashmir, Srinagar, 190006, J&K, India.
Funct Integr Genomics. 2025 Mar 1;25(1):50. doi: 10.1007/s10142-025-01552-x.
Cell death plays a significant role in the physiology of all living organisms, and its disruption is the underlying cause of various diseases. Previously, it was assumed that apoptosis and necrosis were the only means of cell death. Recent discoveries of alternative cell death pathways highlighted a complicated interplay between cell death regulation and its role in numerous human pathologies. DNA methylation is a universal epigenetic mechanism characterized by the covalent addition of a methyl group to cytosine in CpG dinucleotides. Alterations in DNA methylation patterns lead to the dysregulation of multiple cell death pathways. DNA methylome studies on cell death pathways have improved our understanding of the mechanism of various types of cell death, such as apoptosis, pyroptosis, necroptosis, ferroptosis, anoikis, autophagy, and cuproptosis. The irregular DNA methylation patterns of genes encoding proteins linked to multiple cell death pathways could underlie resistance to cell death. Dysregulation of cell death is linked to ailments in humans, such as cancer. However, unlike genetic alterations, DNA methylation is reversible, making it extremely interesting for therapeutics considering the potential use of DNA methyltransferase inhibitors. Furthermore, tumor microenvironment and genetic heterogeneity of cancers may influence the methylation-dependent regulation of cell death, contributing to tumor progression and therapeutic resistance. Understanding how DNA methylation influences cell death pathways may illuminate the underlying causes of cancer. This review explores the significance of the DNA methylation patterns of key genes involved in cell death pathways, emphasizing their connections and identifying potential gaps that could be exploited for developing epigenetic therapies targeting cancer.
细胞死亡在所有生物体的生理过程中发挥着重要作用，其紊乱是多种疾病的根本原因。以前，人们认为凋亡和坏死是细胞死亡的唯一方式。最近对其他细胞死亡途径的发现凸显了细胞死亡调控与其在众多人类病理中的作用之间复杂的相互作用。DNA甲基化是一种普遍的表观遗传机制，其特征是在CpG二核苷酸中的胞嘧啶上共价添加一个甲基基团。DNA甲基化模式的改变会导致多种细胞死亡途径的失调。对细胞死亡途径的DNA甲基化组研究增进了我们对各种类型细胞死亡机制的理解，如凋亡、焦亡、坏死性凋亡、铁死亡、失巢凋亡、自噬和铜死亡。与多种细胞死亡途径相关的蛋白质编码基因的不规则DNA甲基化模式可能是细胞死亡抗性的基础。细胞死亡失调与人类疾病如癌症有关。然而，与基因改变不同，DNA甲基化是可逆的，考虑到DNA甲基转移酶抑制剂的潜在用途，这使其在治疗方面极具吸引力。此外，癌症的肿瘤微环境和基因异质性可能影响细胞死亡的甲基化依赖性调控，促进肿瘤进展和治疗抗性。了解DNA甲基化如何影响细胞死亡途径可能会阐明癌症的潜在病因。本综述探讨了参与细胞死亡途径的关键基因的DNA甲基化模式的重要性，强调它们之间的联系，并确定可能用于开发针对癌症的表观遗传疗法的潜在空白。
