非复制型腺病毒携带miR-1的表达诱导肝癌细胞凋亡

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.

Exprssion of miR-1 mediated by replication-defcient adenovirus induces apoptosis in Cultured Hepatocellular Carcinoma Cells

Downregulation of miR-1 was reported in human hepatocellular 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-defcient adenoviral vector(Ad-miR-1),to evaluate the antitumor activity of miR-1. 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 downregulation of 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 maybe a important aiticancer factor in hepatocellular carcinoma cells.We also concluded that expression of therapeutic microRNA, such as miR-1, via adenoviral vector is a promising strategy for research of gene therapy.