由于起病隐匿，多数肝细胞肝癌（HCC）患者诊断时已不能手术，放疗是其重要治疗手段之一。但是HCC本身的放疗抵抗性严重影响放疗疗效。我们前期研究发现HCC细胞株在放射后出现放疗抵抗，同时miRNA表达谱明显变化，其中miR-92b在各细胞系中均显著下降；RAD21(同源重组修复基因21)和p57kip2是miR-92b的靶基因；而且放射后肝癌细胞中G0/G1 期细胞的比例明显增高。由此提出科学假说：miR-92b可能（1）通过RAD21影响DNA放射损伤修复，降低HCC放射敏感性，（2）通过负调控p57kip2，使细胞周期阻滞于G1期，即放疗抵抗期。本项目拟在细胞、分子水平研究miR-92b在DNA损伤修复（miR-92b-RAD21通路）和细胞周期调控（miR-92b-p57kip2通路）协同作用HCC放疗敏感性的机制，并在动物体内尝试高表达miR-92b以增强HCC放疗疗效。

Because of hidden onset, most of the HCC patients are not suitable to receive surgery resection when diagnosis. Radiotherapy is one of the important non-surgery treatments, but the therapy effect is impaired by radioresistance of HCC cells. In our preliminary study, we detected radioresistance of HepG2、 H22，SMMC-7721 cells after exposed to single 6Gy irraditaion and miR-92b was dramatically downregulated. Meanwhile, the proportion of cells in G0/G1 phase increased significantly. Thus we hypothesized that downexpressed miR-92b may influence radiosensitivity of HCC cells by (1) targeting RAD21 (one of the important gene in homologous recombination repair pathway) to regulate the radiation-caused DNA damage repair, and (2) targeting p57kip2 (cyclin-dependent kinase inhibitor gene in G1/S checkpoint), which arrest the cell cycle in G1 phase in which the cells are resisted to radiotherapy. Therefore, the main purpose of this project is to explore the effects of miR-92b-RAD21 and miR-92b- p57kip2 pathways on radioresistance of HCC cells and the specific regulation mechanism in vitro. Then we will enhance expression of miR-92b in vivo in order to improve the therapeutic effect of radiation on transplanted HCC.