mRNA m6A甲基化修饰对干细胞生物学特性的影响  

Progress in studies on biological properties of stem cells modified by mRNA m6A methylation

作　　者：韩韦钰 赵永超 赵然尊 Han Weiyu;Zhao Yongchao;Zhao Ranzun(Department of Cardiology,Affiliated Hospital of Zunyi Medical University,Zunyi 563000,Guizhou Province,China)

机构地区：[1]遵义医科大学附属医院心血管内科,贵州省遵义市563000

出　　处：《中国组织工程研究》2023年第10期1584-1592,共9页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(81960066),项目负责人:赵然尊;贵州省科技厅基础研究计划项目(黔科合基础-ZK[2022]一般671),项目负责人:赵永超。

摘　　要：背景:干细胞具有自我更新和多能定向分化潜能,是机体维持生理功能所必须的,并在多种疾病发生发展以及疾病治疗与器官移植等方面具有重要意义。近年研究发现m6A甲基化修饰可调控干细胞生物学特性在多种疾病中发挥重要作用。目的:文章主要就m6A甲基化修饰对干细胞的自我更新、定向分化以及其免疫学特性等生物学过程的最新研究进展进行综述。方法:以“stem cells,m6A,RNA methylation,biological characteristics,self-renewal,proliferation,differentiation,immunization”为英文检索词,以“干细胞、m6A、甲基化、生物学特性、自我更新、增殖、分化、免疫”为中文检索词,检索Pub Med、Web of Science以及中国知网数据库1955-2022年的相关文献,最后纳入88篇文献进行综述。结果与结论:m6A作为真核生物m RNA中丰度最高的表观遗传学修饰,也是当前表观遗传学研究的热点,由甲基转移酶、去甲基化酶和甲基阅读蛋白组成,已成为一种重要的转录组标记。m6A甲基化修饰调控干细胞生物学特性方面得出以下结论:(1)m6A甲基化修饰可通过相关的酶靶向调节细胞周期转化、增殖相关分子的转录后翻译、DNA复制过程中关键酶的表达、向特定细胞的分化、免疫检查点分子的表达以及对放化疗药物的敏感性等,进而在治疗恶性疾病、延缓病情、改善预后发挥着关键作用。(2)m6A相关酶分子与干细胞的增殖与自我更新、定向分化以及免疫调节方面的生物学特性关系密切,可作为药物治疗的靶标。(3)m6A甲基化修饰对人类疾病的研究尚处于基础研究阶段,且部分恶性疾病的m6A修饰机制尚未深入探究清楚,随着表观遗传学的发展,RNA m6A修饰在治疗恶性疾病以及临床转化过程中有望实现新的突破。BACKGROUND:Stem cells have the potential of self-renewal and pluripotent directional differentiation,which are necessary for the body to maintain physiological functions,and play an important role in the occurrence and development of various diseases,disease treatment and organ transplantation.Recent studies have found that m6A methylation modification can regulate the biological characteristics of stem cells and play an important role in various diseases.OBJECTIVE:To mainly summarize the latest research progress of biological process of m6A methylation modification of stem cells,including self-renewal,directional differentiation,and immunological characteristics.METHODS:Related articles published from 1955 to 2022 were retrieve from PubMed,Web of Science and CNKI databases.The keywords were “stem cell,m6A,RNA methylation,biological characteristics,self-renewal,proliferation,differentiation,immunization” in English and Chinese.Ultimately,we included 88articles for review.RESULTS AND CONCLUSION:m6A,as the epigenetic modification with the highest abundance in eukaryotic mRNA,is also the focus of current epigenetic research.It is composed of methyltransferase,demethylase and methyl-binding domain protein,and has become an important transcriptome marker.The conclusions of m6A methylation regulate the biological characteristics as following:(1) m6A methylation modification can be adjusted by related enzymes target transformation,proliferation,cell cycle-related molecular transcription after translation,the expression of key enzymes in the process of DNA replication,to a particular cell differentiation,immune checkpoint molecular expression and their sensitivity to radiation and chemotherapy drugs,and in the treatment of malignant disease,delay condition,improve the prognosis of playing a key role.(2) m6A-related enzymes are closely related to the biological characteristics of stem cell proliferation,self-renewal,directed differentiation and immune regulation,and can be used as a target for drug therapy.(3) The stu

关 键 词：m6A 表观遗传 干细胞 自我更新 定向分化 免疫学特性 转录组标记 综述 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学] R364