TET酶家族在神经胶质瘤干细胞中的分化调控机制及其潜在治疗靶点的研究进展  

Research progress of TET family enzymes in the differentiation regulation mechanism of glioma stem cells and its potential therapeutic targets

作　　者：傅雨昂 魏子龙 FU Yu-ang;WEI Zi-long(Department of Neurosurgery,Shanghai Pudong Hospital-Fudan University Pudong Medical Center,Shanghai 201399,China;Undergraduate of Grade 2018 of Preventive Medicine,School of Public Health,Fudan University,Shanghai 200032,China)

机构地区：[1]上海市浦东医院-复旦大学附属浦东医院神经外科,上海201399 [2]复旦大学公共卫生学院,上海200032

出　　处：《复旦学报（医学版）》2022年第5期771-776,807,共7页Fudan University Journal of Medical Sciences

基　　金：上海市浦东新区卫生系统学科带头人培养计划(PWRd2019-15)。

摘　　要：神经胶质瘤干细胞(glioma stem cell,GSC)是神经系统肿瘤组织中具有干细胞基本特性的细胞,具有多向分化潜能,其不对称分化导致的表观遗传修饰异质性有望成为基础研究和临床精准治疗的关键因素。TET酶家族被认为是抑癌基因的重要表达产物之一,其功能紊乱与神经胶质瘤发生相关,TET酶家族介导的DNA去甲基化过程及其表观修饰产物是治疗和诊断多形性胶质母细胞瘤(glioblastoma multiforme,GBM)的关键切入点。目前关于TET酶家族在GSC分化调控中的作用结论尚不一致。本文对TET酶家族在GSC分化过程中通过去甲基化调控基因表达的具体机制及其在DNA损伤应答和修复过程的作用加以阐述,进而说明TET酶家族表达缺失对GSC致瘤性和耐药性的影响,并对干预TET酶家族及其上游基因的功能治疗神经胶质瘤进行展望。Glioma stem cells(GSCs)are a part of cells with the basic characteristics of stem cells in the tumor tissues of the nervous system,and have the potential of multidirectional differentiation.The heterogeneity of epigenetic modification caused by asymmetric differentiation will also become a key factor in basic research and clinical precision therapy.The TET family enzymes are generally regarded as one of the important expression products of tumor suppressor genes,and its dysfunction is related to the occurrence of glioma.TET-mediated DNA demethylation process and its epigenetic modification products are the key entry point for the treatment and diagnosis of glioblastoma.Currently,findings about the role of the TET family enzymes in the regulation of GSC differentiation are not consistent.Therefore,in this paper,the specific mechanism of the TET family enzymes regulating gene expression through methylation in the process of GSC differentiation and its role in the DNA damage response and repair process are described,and then the influence of the loss of the TET family enzymes expression on tumorigenicity and drug resistance of GSC is explained.An outlook on the potential therapeutic methods for glioma by interfering the function of TET family enzymes and its upstream genes is presented.

关 键 词：神经胶质瘤干细胞(GSC) TET酶家族 表观遗传修饰异质性 分化调控 靶向治疗 

分 类 号：R651.1[医药卫生—外科学]