非复制型腺病毒携带miR-1的表达诱导肝癌细胞凋亡  

Expression of miR-1 Mediated by Replication-deficient Adenovirus Induces Apoptosis in Cultured Hepatocellular Carcinoma Cells

作　　者：李伟[1] 王秀敏[1] 吴亦栋[1] 陈学军[1] 魏旭斌[2] 楼金吐[1] 彭朝阳[1] 董敖[1] 杨樱之[3] 尚世强[1] 

机构地区：[1]浙江大学医学院附属儿童医院中心实验室,杭州310003 [2]浙江理工大学生命科学院新元医学与生物技术研究所,杭州310018 [3]浙江大学城市学院,杭州310015

出　　处：《中国生物化学与分子生物学报》2013年第9期873-879,共7页Chinese Journal of Biochemistry and Molecular Biology

基　　金：浙江省自然科学基金项目(No.Y2100891);浙江省医药卫生一般计划项目(No.2009B097);浙江省科技厅研究项目(No.2011C33036)~~

摘　　要：miR-1在多种肝癌细胞中被甲基化沉默,导致其下游多个癌基因MET,FoxP1,HDAC4等大量表达,促进了肝癌的增殖.本研究利用非复制型腺病毒Ad-easy携带miR-1(Ad-miR-1)在肝癌细胞PLC/PRF/5和HepG2中过表达miR-1,探讨miR-1抑制肝癌细胞的作用机制.结果表明,肝癌细胞PLC/PRF/5和HepG2中miR-1表达水平极低,感染Ad-miR-1后miR-1表达水平显著上升.肝癌细胞PLC/PRF/5和HepG2感染Ad-miR-1后,MET和FoxP1的mRNA水平和蛋白表达水平被显著下调,细胞凋亡水平显著增加,肝癌细胞的增殖被抑制.可见,miR-1在肝癌细胞中可能是一个重要的抑癌因子.同时,利用腺病毒载体携带抗癌的microRNA(如miR-1),也为今后的基因治疗研究提供了一种新方法.Downregulation of miR-1 was reported in human hepatoeellular carcinoma with high expression of MET,FoxP1, HDAC4. In this study, we presented a strategy for cancer therapy based on gene transfer of miR-1 by replication-deficient adenoviral vector （Ad-miR-1） to evaluate the antitumor activity of miR-l. Our data showed that Ad-miR-1 could express functional miR-1 in PLC/PRF/5 cells and HepG2 cells at a high level with downregulated MET and FoxP1 expression. Infection of hepatocellular carcinoma cells with Ad-miR-1 resulted in inhibition of proliferation of cancer cells and induced cells apoptosis. In conclusion, miR-1 might be an important anticancer factor in hepatocellular carcinoma cells. We also concluded that expression of therapeutic microRNA, such as miR-1, via adenoviral vector was a promising strategy for research of gene therapy.

关 键 词：Ad—easy MIR-1 肝癌细胞 凋亡 

分 类 号：Q78[生物学—分子生物学]