Shah Vandit, Lam Hiu Yan, Leong Charlene Hoi-Mun, Sakaizawa Reo, Shah Jigna S, Kumar Alan Prem
Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, India.
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Antioxid Redox Signal. 2025 Jun;42(16-18):848-867. doi: 10.1089/ars.2023.0465. Epub 2025 Jan 16.
Growing evidence indicates the importance of redox reactions homeostasis, mediated predominantly by reactive oxygen species (ROS) in influencing the development, differentiation, progression, metastasis, programmed cell death, tumor microenvironment, and therapeutic resistance of cancer. Therefore, reviewing the ROS-linked epigenetic changes in cancer is fundamental to understanding the progression and prevention of cancer. We review in depth the molecular mechanisms involved in ROS-mediated epigenetic changes that lead to alteration of gene expression by altering DNA, modifying histones, and remodeling chromatin and noncoding RNA. In cancerous cells, alterations of the gene-expression regulatory elements could be generated by the virtue of imbalance in tumor microenvironment. Various oxidizing agents and mitochondrial electron transport chain are the major pathways that generate ROS. ROS plays a key role in carcinogenesis by activating pro-inflammatory signaling pathways and DNA damage. This loss of ROS-mediated epigenetic regulation of the signaling pathways may promote tumorigenesis. We address all such aspects in this review. Developments in this growing field of epigenetics are expected to contribute to further our understanding of human health and diseases such as cancer and to test the clinical applications of redox-based therapy. Recent studies of the cancer-epigenetic landscape have revealed pervasive deregulation of the epigenetic factors in cancer. Thus, the study of interaction between ROS and epigenetic factors in cancer holds a great promise in the development of effective and targeted treatment modalities. 42, 848-867.
越来越多的证据表明，主要由活性氧（ROS）介导的氧化还原反应稳态在影响癌症的发生、发展、分化、进展、转移、程序性细胞死亡、肿瘤微环境和治疗耐药性方面具有重要意义。因此，回顾癌症中与ROS相关的表观遗传变化对于理解癌症的进展和预防至关重要。我们深入综述了ROS介导的表观遗传变化所涉及的分子机制，这些变化通过改变DNA、修饰组蛋白、重塑染色质和非编码RNA导致基因表达改变。在癌细胞中，肿瘤微环境的失衡可能导致基因表达调控元件的改变。各种氧化剂和线粒体电子传递链是产生ROS的主要途径。ROS通过激活促炎信号通路和DNA损伤在致癌过程中起关键作用。这种ROS介导的信号通路表观遗传调控的丧失可能促进肿瘤发生。我们在本综述中探讨了所有这些方面。表观遗传学这一不断发展的领域的进展有望进一步促进我们对人类健康和癌症等疾病的理解，并测试基于氧化还原的治疗方法的临床应用。最近对癌症表观遗传格局的研究揭示了癌症中表观遗传因子的普遍失调。因此，研究癌症中ROS与表观遗传因子之间的相互作用在开发有效和靶向治疗方法方面具有巨大潜力。42, 848 - 867。
