原发性肝癌严重危害人类健康且对化疗敏感性低。研究证实上调miR-34a能增加肿瘤细胞的化疗敏感性。FAT10通过调控下游底物参与肿瘤的发生发展。我们前期研究发现在p53缺失的肝癌细胞中降低FAT10，能增加miR-34a的表达从而提高肝癌细胞的化疗敏感性。同时我们研究还发现上调FAT10能抑制p53表达从而下调miR-34a，保护心肌细胞免受由缺血缺氧引起的凋亡。综合以上结果，我们推测在肝癌细胞中，FAT10调控miR-34a而影响其化疗敏感性的通路中存在不依赖p53的调控途径。本课题首先明确FAT10调控miR-34a从而影响肝癌的化疗敏感性；然后观察FAT10表达变化时，顺铂对不同状态p53肝癌细胞化疗敏感性的影响及生物学特性的改变，并利用体外研究进一步证实。明确FAT10通过不依赖p53途径调控肝癌化疗敏感性，从而提供新的特异性药物治疗靶点，并为调节肝癌化疗敏感性提供理论依据。

Primary hepatocellular carcinoma(PHC) seriously threatens to people health with low sensitivity to chemotherapy. It confirmed the upregulation of miR-34a can increase the chemosensitivity of tumor cells. FAT10 can regulate the occurrence and development of tumor through downstream substrates. Our previous study found it can increase the expression of miR-34a by down-regulating of FAT10 then increasing the chemosensitivity of hepatocellular carcinoma cells with p53 dyfunction. At the same time, we also found that the up-regulation of FAT10 could inhibit the expression of p53 and downregulation of miR-34a to protect myocardial cells from apoptosis caused by ischemia and hypoxia. Based on the above results, We hypothesize that FAT10 regulates miR-34a to effect the chemosensitivity of hepatocellular carcinoma cells independent p53.In this study:Firstly,It confirmes the FAT10 regulation of miR-34a can influence the sensitivity of chemotherapy for hepatocellular carcinoma; then observes the effect of cisplatin on chemosensitivity of human hepatocellular carcinoma cells and the change of its biological characteristics with changing expression of FAT10 on different state of p53.A in vitro study is use to further confirmed. Elucidate the FAT10 regulation of liver cancer chemotherapy sensitivity path by independent of p53,which provides the possibility of enhancing the therapeutic effect of both chemotherapyand the future generation of targeted anticancer agents.