use of microrna let-7 to control the replication specificity of oncolytic adenovirus in hepatocellular carcinoma cells使用微let-7控制复制在肝癌细胞特异性溶瘤腺病毒.pdfVIP

Use of MicroRNA Let-7 to Control the Replication Specificity of Oncolytic Adenovirus in Hepatocellular Carcinoma Cells 1,2. 1. 1. 2 1 1 Huajun Jin , Saiqun Lv , Jiahe Yang , Xiaoning Wang , Huanzhang Hu , Changqing Su , Chengliang 1 1 1 1 3 1 1,3 Zhou , Jiang Li , Yao Huang , Linfang Li , Xinyuan Liu , Mengchao Wu , Qijun Qian * 1 Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China, 2 School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, Guangdong Province, China, 3 College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang Province, China Abstract Highly selective therapy for hepatocellular carcinoma (HCC) remains an unmet medical need. In present study, we found that the tumor suppressor microRNA, let-7 was significantly downregulated in a proportion of primary HCC tissues (12 of 33, 36.4%) and HCC cell lines. In line with this finding, we have engineered a chimeric Ad5/11 fiber oncolytic adenovirus, SG7011let7T, by introducing eight copies of let-7 target sites (let7T) into the 3 9 untranslated region of E1A, a key gene associated with adenoviral replication. The results showed that the E1A expression (both RNA and protein levels) of the SG7011let7T was tightly regulated according to the endogenous expression level of the let-7. As contrasted with the wild-type adenovirus and the control virus, the replication of SG7011let7T was distinctly inhibited in normal liver cells lines (i.e. L-02 and WRL-68)