Aberrant DNA methylation as a key modulator of cell death pathways: insights into cancer progression and other diseases

IF 3.9 4区 生物学 Q1 GENETICS & HEREDITY
Ambreen Zahoor, Rafia Khazer, Insha Mehraj, Ubaid Gani, Falah Fayaz, Firdous A. Khanday, Sahar Saleem Bhat
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Abstract

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.

DNA甲基化异常是细胞死亡通路的关键调节因子:对癌症进展和其他疾病的启示
细胞死亡在所有生物的生理中起着重要的作用,细胞死亡的破坏是各种疾病的根本原因。以前,人们认为细胞凋亡和坏死是细胞死亡的唯一方式。最近发现的替代细胞死亡途径强调了细胞死亡调节及其在许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CpG二核苷酸中胞嘧啶共价添加一个甲基。DNA甲基化模式的改变导致多种细胞死亡途径的失调。DNA甲基组对细胞死亡途径的研究提高了我们对各种类型细胞死亡机制的理解,如凋亡、焦亡、坏死、铁亡、anoikis、自噬和铜腐。编码与多种细胞死亡途径相关的蛋白质的基因的不规则DNA甲基化模式可能是抵抗细胞死亡的基础。细胞死亡失调与癌症等人类疾病有关。然而,与遗传改变不同,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,这使得它对治疗学非常有趣。此外,肿瘤微环境和癌症的遗传异质性可能影响细胞死亡的甲基化依赖性调节,促进肿瘤进展和治疗耐药性。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原因。这篇综述探讨了参与细胞死亡途径的关键基因的DNA甲基化模式的意义,强调了它们之间的联系,并确定了可能用于开发针对癌症的表观遗传疗法的潜在空白。
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来源期刊
CiteScore
3.50
自引率
3.40%
发文量
92
审稿时长
2 months
期刊介绍: Functional & Integrative Genomics is devoted to large-scale studies of genomes and their functions, including systems analyses of biological processes. The journal will provide the research community an integrated platform where researchers can share, review and discuss their findings on important biological questions that will ultimately enable us to answer the fundamental question: How do genomes work?
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