无义介导的mRNA降解机制在肿瘤发生和治疗中的功能研究进展  

Research progresses of nonsense-mediated mRNA decay in tumorigenesis and cancer therapy

作　　者：汪宇慧 王京鹏 陈贝[2] 王亚茹[2] 李唐亮 WANG Yuhui;WANG Jingpeng;CHEN Bei;WANG Yaru;LI Tangliang(School of Basic Medical Sciences,Hangzhou Normal University,Hangzhou 311121,Zhejiang,China;State Key Laboratory of Microbial Technology,Shandong University,Qingdao 266237,Shandong,China)

机构地区：[1]杭州师范大学基础医学院,浙江杭州311121 [2]山东大学微生物技术国家重点实验室,山东青岛266237

出　　处：《中国临床药理学与治疗学》2024年第8期930-936,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：2023年山东省自然科学基金面上项目(ZR2023MC013);2023年青岛市自然科学基金原创探索项目(23-2-1-167-zyyd-jch)。

摘　　要：无义介导的mRNA降解(nonsense-mediated mRNA decay,NMD)是广泛存在于真核生物细胞的转录后调控机制,可以识别并降解含有提前终止密码子(premature termination codons,PTC)的异常转录本,防止截短蛋白积累,同时NMD可以降解一些正常可以翻译为功能蛋白的mRNA分子,精准调控基因表达。NMD的生物学功能集中在细胞命运调控、细胞应激反应与动物胚胎发育等过程。本综述对无义介导的mRNA降解通路激活和抑制在肿瘤发生、发展和治疗中的功能及分子机制进行简要探讨。现有研究指出,NMD因子突变可导致人类多种肿瘤的发生。有意义的是,抑制NMD因子的表达,可以通过激活DNA损伤反应和抑制促癌因子的表达,起到杀灭癌症细胞的功效。本综述可为人类癌症发生的生物学机制和治疗策略提供新的思路。Nonsense-mediated mRNA decay(NMD)is a highly conserved post-transcriptional regulatory mechanism in eukaryotic cells.NMD can recognize and degrade abnormal transcripts containing premature termination codons(PTC)to prevent the translation of C-terminal truncated proteins.Furthermore,NMD could degrade a subset of normal gene transcripts and thus fine-tune gene expression.NMD is essential for cell fate determination,stress response,as well as animal development.In this review,we briefly discussed the functional and molecular mechanisms of NMD pathway activation and inhibition in tumorigenesis,cancer progression and therapy.Current studies indicate that NMD factor mutations can lead to a variety of human tumors.Interestingly,inhibition of NMD factors can activate DNA damage response and inhibit the expression of oncogenic factors,thereby killing cancer cells.This review may provide new perspectives for the biological mechanism and therapeutic strategy of human tumors.

关 键 词：无义介导的mRNA降解 肿瘤 DNA损伤反应 炎症 

分 类 号：R73[医药卫生—肿瘤]