RNA甲基化修饰调控DNA损伤修复过程及其在肿瘤耐药中的作用
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1.安徽医科大学第一临床医学院;2.安徽医科大学生命科学学院

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Regulation of RNA methylation modifications during DNA damage repair and their roles in tumor drug resistance
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    摘要:

    DNA损伤修复是指纠正DNA两条单链间错配的碱基、清除DNA链上受损的碱基、恢复DNA正常结构的过程。细胞内存在多种机制对不同类型的DNA损伤进行修复,其中同源重组修复过程涉及新生RNA的合成,因此真核细胞中广泛存在的RNA甲基化修饰也参与了这一过程的调控。在肿瘤发生过程中,普遍存在着RNA甲基化修饰的失调从而导致的DNA损伤的累积,进而引起恶性转化。另一方面,RNA甲基化修饰还通过调节放化疗后细胞DNA的损伤修复,使肿瘤细胞发生放化疗敏感性的改变,进而影响治疗效果。本文综述了目前已知的不同类型RNA甲基化修饰在DNA损伤修复过程中发挥的作用,并进一步分析了RNA甲基化修饰介导的DNA损伤修复异常在肿瘤的临床诊断、预后判断和作为治疗靶点等方面应用前景。

    Abstract:

    As one of the hallmarks of cancer cell, genomic instability induced by continuously endogenous and exogenous stress, lead to the application of radiotherapy and chemotherapy in cancer treatment. Several DNA damage repair pathways have been developed to cope with the frequent challenge of DNA insults, including Homologous recombination (HR), which comprises a series of protein complexes and nascent RNAs to repair DNA double-stranded breaks (DSBs), and the prevalent RNA methylation modifications in eukaryotic cells inevitably involve in the regulation of DNA damage repair. Thereby, aberrant RNA methylation modifications in cancer cells lead to the increasing accumulations of DNA damage, and on the other hand mediate the resistance of chemotherapy and radiotherapy. In the current review, we summarize the types of RNA methylation modifications and their roles in the process of DNA damage repair, and further discuss their application prospects in the clinical diagnosis, prognosis and therapeutic targets of tumors.

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历史
  • 收稿日期:2022-12-02
  • 最后修改日期:2024-04-25
  • 录用日期:2023-02-21
  • 在线发布日期: 2024-07-19
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