周建生,等.DNA甲基化/去甲基化与癌症·381·收稿日期：2012-10-04第一作者：周建生(1988-)，男，硕士生，E-mail:zhoujiansheng0902@163.com*通信作者：焦炳华(1962-)，男，博士，教授，E-mail:jiaobh@uninet.com.cn生命的化学,2013,33(4):381-388www.life.ac.cn综述DNA甲基化/去甲基化与癌症周建生，杨生生，缪明永，焦炳华*(第二军医大学基础部生物化学与分子生物学教研室，上海200433)摘要：DNA甲基化是真核细胞基因组中常见的可遗传的表观遗传修饰，在调节细胞增殖、分化、个体发育等方面起重要作用，并且DNA甲基化水平异常与肿瘤的发生发展密切相关。DNA甲基化及被动去甲基化主要是在DNA甲基转移酶家族参与下完成的，而DNA的主动去甲基化机制尚不是很明确。在肿瘤细胞中DNA的整体甲基化水平显著降低，但抑癌基因的启动子区域却出现高甲基化。目前尽管有DNA去甲基化药物用于癌症的临床治疗，但药物特异性较差，因而研究特定基因的主动去甲基化机制有助于研发特异性高的药物用于癌症的治疗。关键词：DNA甲基化；DNA去甲基化；癌症；表观遗传治疗RelationshipbetweenDNAmethylation/demethylationandcancerZHOUJiansheng,YANGShengsheng,MIAOMingyong,JIAOBinghua*(DepartmentofBiochemistryandMolecularBiology,CollegeofBasicMedicalSciences,theSecondMilitaryMedicalUniversity,Shanghai200433,China)Abstract:DNAmethylation,themostcommonheritableepigeneticmarkerofeukaryotegenome,playsacriticalroleincellproliferation,differentiation,anddevelopment.AberrantDNAmethylationiscorrelatedwiththeonsetandprogressionofcancer.ItiswellacceptedthatDNAmethylationandDNApassivedemethylationaremainlycatalyzedbythefamilyofDNAmethyltransferases.However,themechanismofDNAactivedemethylationisunclear.Incancercells,theglobalgenomiclevelsofDNAmethylationarelower,butthepromotermethylationlevelsoftumorsuppressorgenesarehigherthaninnormaltissues.Severaldemethylatingagentshavebeenappliedfortheclinicaltreatmentofcancer,buttheseagentsarelackofspecificityfortargetgenes.Sostudyingthemechanismofactivedemethylationofspecificgenesavailstheresearchanddevelopmentofhigh-specificityagentsforthetreatmentofcancer.Keywords:DNAmethylation;DNAdemethylation;cancer;epigenetictherapy表观遗传的概念最初是由Co...
