m6A修饰对于肿瘤在传统化疗和新型靶向治疗耐药中的作用研究进展  

The research progress of m6A modification on the drug resistance of tumors in traditional chemotherapy and New targeted therapies

作　　者：郑思晴 王昊[2] ZHENG Siqing;WANG Hao(School of Pharmacy,Anhui Medical University,Hefei 230000)

机构地区：[1]安徽医科大学药学院,安徽合肥230000 [2]中国科学技术大学附属第一医院(安徽省立医院)检验科,安徽合肥230001

出　　处：《临床输血与检验》2023年第5期706-720,共15页Journal of Clinical Transfusion and Laboratory Medicine

基　　金：安徽省教育厅高校科研计划杰出青年基金项目(No.2022AH020079)资助。

摘　　要：近年来,癌症治疗取得了巨大进步,显著提高了临床疗效。然而,肿瘤耐药一直是影响癌症治疗效果的关键问题,其复杂的机制仍然难以捉摸。N6-甲基腺苷(m6A)修饰作为表观遗传学研究的热点,被认为是克服耐药的潜在靶点,受到越来越多的关注。作为最常见的RNA修饰方式,m6A参与了RNA剪接、核输出、翻译、稳定性等RNA代谢的各个环节。m6A甲基转移酶(writer),去甲基化酶(eraser)和RNA结合蛋白(reader)这三类调控分子共同协调m6A修饰的动态和可逆过程。本文主要综述了m6A修饰在肿瘤化疗和靶向治疗耐药中的作用及调控机制,并探讨m6A修饰在克服肿瘤化疗耐药和优化癌症治疗方面的临床潜力,同时展望了m6A修饰的未来研究方向。Objective Marvelous advancements have been made in cancer therapies to improve clinical outcomes over last few years.However,therapeutic resistance has always been a major difficulty in cancer therapy,with extremely complicated mechanisms remain elusive.N6-methyladenosine(m6A)RNA modification,a hotspot in epigenetics,has gained growing attention as a potential determinant of therapeutic resistance.As the most prevalent RNA modification,m6A is involved in every links of RNA metabolism,including RNA splicing,nuclear export,translation and stability.Three kinds of regulators,methyltransferase(writer),demethylase(eraser)and RNA binding proteins(reader),together orchestrate the dynamic and reversible process of m6A modification.Herein,we primarily reviewed the regulatory mechanisms of m6A in therapeutic resistance,including chemotherapy and targeted therapy.Then we discussed the clinical potential of m6A modification to overcome resistance and optimize cancer therapy.Additionally,we proposed prospects of m6A modification for future research.

关 键 词：癌症治疗 m6A 化疗耐药 靶向治疗耐药 

分 类 号：R730.5[医药卫生—肿瘤]