Zhang Shunhao, Duan Sining, Xie Zhuojun, Bao Wanlin, Xu Bo, Yang Wenbin, Zhou Lingyun
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Department of Stomatology, Panzhihua Central Hospital, Panzhihua, China.
Front Pharmacol. 2022 Jun 9;13:924817. doi: 10.3389/fphar.2022.924817. eCollection 2022.
The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) and its negative regulator kelch-like ECH-associated protein 1 (KEAP1) regulate various genes involved in redox homeostasis, which protects cells from stress conditions such as reactive oxygen species and therefore exerts beneficial effects on suppression of carcinogenesis. In addition to their pivotal role in cellular physiology, accumulating innovative studies indicated that NRF2/KEAP1-governed pathways may conversely be oncogenic and cause therapy resistance, which was profoundly modulated by epigenetic mechanism. Therefore, targeting epigenetic regulation in NRF2/KEAP1 signaling is a potential strategy for cancer treatment. In this paper, the current knowledge on the role of NRF2/KEAP1 signaling in cancer oxidative stress is presented, with a focus on how epigenetic modifications might influence cancer initiation and progression. Furthermore, the prospect that epigenetic changes may be used as therapeutic targets for tumor treatment is also investigated.
转录因子核因子红系2相关因子2（NRF2）及其负调控因子kelch样ECH相关蛋白1（KEAP1）调控参与氧化还原稳态的各种基因，氧化还原稳态可保护细胞免受活性氧等应激条件的影响，从而对抑制肿瘤发生发挥有益作用。除了在细胞生理学中发挥关键作用外，越来越多的创新性研究表明，NRF2/KEAP1调控的通路可能反而具有致癌性并导致治疗耐药性，而这受到表观遗传机制的深刻调节。因此，靶向NRF2/KEAP1信号通路中的表观遗传调控是一种潜在的癌症治疗策略。本文介绍了目前关于NRF2/KEAP1信号通路在癌症氧化应激中作用的知识，重点关注表观遗传修饰如何影响癌症的发生和发展。此外，还研究了表观遗传变化作为肿瘤治疗靶点的前景。
