There is accumulating evidence indicating a close crosstalk between key molecular events regulating cell growth and proliferation, which could profoundly impact carcinogenesis and its progression. Here we focus on reviewing observations highlighting the interplay between epigenetic modifications, irreversible cell cycle arrest or senescence, and cellular redox metabolism. Epigenetic alterations, such as DNA methylation and histone modifications, dynamically influence tumour transcriptome, thereby impacting tumour phenotype, survival, growth and spread. Interestingly, the acquisition of senescent phenotype can be triggered by epigenetic changes, acting as a double-edged sword via its ability to suppress tumorigenesis or by facilitating an inflammatory milieu conducive for cancer progression. Concurrently, an aberrant redox metabolism, which is a function of the balance between reactive oxygen species (ROS) generation and intracellular anti-oxidant defences, influences signalling cascades and genomic stability in cancer cells by serving as a critical link between epigenetics and senescence. Recognizing this intricate interconnection offers a nuanced perspective for therapeutic intervention by simultaneously targeting specific epigenetic modifications, modulating senescence dynamics, and restoring redox homeostasis.

中文翻译：

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癌症中表观遗传学、衰老和细胞氧化还原代谢之间的相互作用及其治疗意义


越来越多的证据表明，调节细胞生长和增殖的关键分子事件之间存在密切的交叉影响，这可能会对致癌作用及其进展产生深远影响。在这里，我们重点回顾了突出表观遗传修饰、不可逆细胞周期停滞或衰老以及细胞氧化还原代谢之间的相互作用的观察结果。表观遗传改变，如 DNA 甲基化和组蛋白修饰，动态影响肿瘤转录组，从而影响肿瘤表型、存活、生长和扩散。有趣的是，衰老表型的获得可以由表观遗传变化触发，通过其抑制肿瘤发生的能力或促进有利于癌症进展的炎症环境起到双刃剑的作用。同时，异常的氧化还原代谢是活性氧 （ROS） 生成和细胞内抗氧化防御之间平衡的功能，通过作为表观遗传学和衰老之间的关键联系来影响癌细胞中的信号级联和基因组稳定性。认识到这种错综复杂的相互联系，通过同时靶向特定的表观遗传修饰、调节衰老动力学和恢复氧化还原稳态，为治疗干预提供了微妙的视角。