甲基转移酶对鼻咽癌细胞中DLC-1基因表达的影响  

Effects of Methyltransferase on DLC-1 Gene Expression in Nasopharyngeal Carcinoma Cells

作　　者：冯湘玲[1] 陈欢 刘卫东[1] 张畅[1] 祝斌[1] 王磊[1] 李敏[1] 周文[1] 姚开泰[1,2] 任彩萍[1] 

机构地区：[1]中南大学肿瘤研究所,中国湖南长沙410078 [2]南方医科大学肿瘤研究所,中国广东广州510515

出　　处：《生命科学研究》2014年第4期292-298,共7页Life Science Research

基　　金：国家973项目(2010CB833605);教育部新世纪优秀人才支持计划项目(NCET-10-0790);中南大学杰青培育项目(2010QYZD006);国家自然科学基金项目(30801322;81272972);湖南省自然科学基金项目(10JJ4025);中南大学贵重仪器设备开放共享基金资助项目

摘　　要：肝癌缺失基因-1(deleted in liver cancer-1,DLC-1)在多种肿瘤中呈现表达缺失或表达下调,这种异常表达主要与由DNA甲基转移酶(DNA methyltransferases,DNMTs)参与的启动子区异常甲基化有关。RT-PCR结果显示DLC-1在永生化鼻咽上皮细胞NP69和干扰DNMTs的5-8F细胞中的表达水平较未干扰的鼻咽癌细胞明显升高。甲基化特异性PCR(methylation-specific PCR,MSPCR)结果则表明DLC-1启动子区在表达下调或缺失的鼻咽癌细胞中均存在异常高甲基化,而干扰DNMTs后5-8F细胞中DLC-1启动子区甲基化状态被逆转,其中特异性干扰DNMT1后效果略为显著,提示DNA甲基转移酶活性对于鼻咽癌中DLC-1启动子区甲基化水平具有重要的调控作用,而DNMT1的调控作用更为突出。Deleted in liver cancer-1（DLC-1） shows loss of expression or down-regulation of expression in a variety of tumors because of promoter hypermethylation with DNA methyltransferases（DNMTs）. RT-PCR results showed DLC-1 expression were higher in control nasopharyngeal cell line NP69 and 5-8F cells which was knockdown of DNMT1, DNMT3 A and DNMT3 B than all 7 NPC cell lines. The promoter hypermethylation of DLC-1 was detected in all 7 NPC cell lines but the DLC-1 promoter could be partially demethylated in 5-8F cells with knockdown of DNMTs, especially DNMT1 with more signifecant effect. Thus, our data suggested that DNMTs, esp. DNMT1, might play important roles in methylation maintenance of DLC-1 in NPC.

关 键 词：DNA甲基转移酶(DNMTs) 肝癌缺失基因-1(DLC-1) 甲基化 RNA干扰 

分 类 号：Q786[生物学—分子生物学]