m^(6)A甲基化修饰在肿瘤中作用的研究进展  

The research progress on m^(6)A RNA methylation in cancer

作　　者：陈蒙蒙 徐克[1] CHEN Mengmeng;XU Ke(Tianjin Medical University General Hospital,Tianjin Lung Cancer Institute,Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment,Tianjin 300052,China;Department of Clinical Laboratory,Shandong Cancer Hospital,Shandong Jinan 250117,China)

机构地区：[1]天津医科大学总医院,天津市肺癌研究所,天津市肺癌转移与肿瘤微环境重点实验室,天津300052 [2]山东省肿瘤医院检验科,山东济南250117

出　　处：《现代肿瘤医学》2023年第7期1352-1358,共7页Journal of Modern Oncology

基　　金：国家自然科学基金(编号:81372519);天津市自然科学基金重点项目(编号:22JCZDJC00450);天津市卫生健康委员会科技项目(编号:TJWJ2021MS006)。

摘　　要：RNA的表观遗传修饰在恶性肿瘤中发挥着重要的调控作用,因此受到人们的广泛关注。N6-甲基腺嘌呤是发生于腺苷N6位上的甲基化修饰,是真核细胞信使RNA上主要的表观遗传修饰。m^(6)A甲基化修饰由m^(6)A甲基转移酶催化,其核心组分包括METTL3、METTL14;由m^(6)A去甲基化酶去除,包括FTO、ALKBH5;并被m^(6)A甲基识别蛋白识别,包括YTHDF1-3、IGF2BP1-3等。m^(6)A甲基化修饰参与RNA代谢的各个阶段,包括:稳定、剪接、出核、翻译和降解等。m^(6)A相关调节蛋白能够通过多种机制调控肿瘤的发生发展:影响m^(6)A甲基化修饰水平,进而在肿瘤细胞增殖、侵袭转移及耐药等过程中发挥重要作用。目前为止,m^(6)A甲基化修饰在人类肿瘤中的作用机制尚未完全阐明。本文概述了m^(6)A修饰的基本功能,并重点介绍其在肿瘤中的作用机制,最后讨论针对肿瘤中m^(6)A修饰的治疗策略。Epigenetic modification of RNA plays an important role in tumor development,so it has drawn intensive attention in recent years.N6-methyladenosine is the methylation that occurs at the N6 position of adenosine,and is the major type of epigenetic modification in eukaryotic messenger RNA.The m^(6)A methylation modification is catalyzed by m^(6)A methyltransferase,and its core components include METTL3 and METTL14.It is removed by m^(6)A demethylase,including FTO and ALKBH5,and it is recognized by m^(6)A methyl recognition proteins,including YTHDF1-3,IGF2BP1-3 and more.m^(6)A methylation is participated in all stages of RNA metabolism,including stabilization,splicing,nuclear export,translation and degradation.m^(6)A-related regulatory proteins can regulate the occurrence and development of tumors through various mechanisms:Affecting the level of m^(6)A methylation modification,and then playing an important role in tumor cell proliferation,invasion and metastasis,and drug resistance.So far,the mechanism of m^(6)A methylation modification in human tumors has not been fully elucidated.This review overviewed the pathological role of m^(6)A modification,in particular,in tumor development.We further discussed the potential therapeutic strategies on targeting m^(6)A modification in tumor treatment.

关 键 词：N6-甲基腺嘌呤 肿瘤 甲基转移酶 去甲基化酶 甲基识别蛋白 

分 类 号：R730[医药卫生—肿瘤]