Chen Xun, Zhang Lejia, He Yi, Huang Siyuan, Chen Shangwu, Zhao Wei, Yu Dongsheng
Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, People's Republic of China.
Guangdong Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory for Biocontrol, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, People's Republic of China.
Cell Death Discov. 2023 Sep 15;9(1):343. doi: 10.1038/s41420-023-01645-1.
Radiotherapy is often used to treat various types of cancers, but radioresistance greatly limits the clinical efficiency. Recent studies have shown that radiotherapy can lead to ferroptotic cancer cell deaths. Ferroptosis is a new type of programmed cell death caused by excessive lipid peroxidation. The induction of ferroptosis provides a potential therapeutic strategy for radioresistance. As the most common post-transcriptional modification of mRNA, mA methylation is widely involved in the regulation of various physiopathological processes by regulating RNA function. Dynamic mA modification controlled by mA regulatory factors also affects the susceptibility of cells to ferroptosis, thereby determining the radiosensitivity of tumor cells to radiotherapy. In this review, we summarize the mechanism and significance of radiotherapy induced ferroptosis, analyze the regulatory characteristics of mA modification on ferroptosis, and discuss the possibility of radiosensitization by enhancing mA-mediated ferroptosis. Clarifying the regulation of mA modification on ferroptosis and its significance in the response of tumor cells to radiotherapy will help us identify novel targets to improve the efficacy of radiotherapy and reduce or overcome radioresistance.
放射疗法常用于治疗各种类型的癌症，但放射抗性极大地限制了临床疗效。最近的研究表明，放射疗法可导致癌细胞发生铁死亡。铁死亡是一种由过度脂质过氧化引起的新型程序性细胞死亡。诱导铁死亡为放射抗性提供了一种潜在的治疗策略。作为mRNA最常见的转录后修饰，m⁶A甲基化通过调节RNA功能广泛参与各种生理病理过程的调控。由m⁶A调控因子控制的动态m⁶A修饰也会影响细胞对铁死亡的敏感性，从而决定肿瘤细胞对放射疗法的放射敏感性。在本综述中，我们总结了放射疗法诱导铁死亡的机制和意义，分析了m⁶A修饰对铁死亡的调控特征，并讨论了通过增强m⁶A介导的铁死亡实现放射增敏的可能性。阐明m⁶A修饰对铁死亡的调控及其在肿瘤细胞对放射疗法反应中的意义，将有助于我们识别新的靶点，以提高放射疗法的疗效并降低或克服放射抗性。
