DNA 甲基化 去甲基化与癌症.pdf

· 381 · 生命的化学, 2013, 33(4): 381-388 周建生, 等. DNA 甲基化/ 去甲基化与癌症 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。 DNA 在肿瘤细胞中 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 Relationship between DNA methylation/demethylation and cancer ZHOU Jiansheng, YANG Shengsheng, MIAO Mingyong, JIAO Binghua* (Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, the Second Military Medical University, Shanghai 200433, China) Abstract: DNA methylation, the most common heritable epigenetic marker of eukaryote genome, plays a critical role in cell proliferation, differentiation, and development. Aberrant DNA methylation is correlated with the onset and progression of cancer. It is well accepted that DNA methylation and DNA passive demethylation are mainly catalyzed by the family of DNA methyltransferases. However, the mechanism of DNA active demethylation is unclear. In cancer cells, the global genomic levels of DNA methylation are lower, but the promoter methylation levels of tumor suppressor genes are higher than in normal tissues. Several demethylating agents have been applied for the clinical treatment of cancer, but these agents are lack of specificity for target genes. So studying the mechanism of active demethylation of specific genes avails the research and development of high-specificity agents for the treatment of cancer. Key word