肝癌发生过程的早期干预对肝癌防治具有重要意义。我们前期研究发现在HBV/HCV感染、NASH、酒精性肝炎等多种诱因引起的人纤维化肝组织和化学诱导的鼠纤维化肝组织中，酪氨酸激酶SYK表达均显著上调；DEN诱导大鼠和四氯化碳诱导小鼠肝纤维化/肝癌模型中，靶向SYK治疗在缓解肝纤维化/肝硬化的同时，能显著减少后期肝癌的发生；进一步小鼠原代肝细胞转录组测序提示：肝纤维化过程中，癌基因MYC伴随SYK表达升高而显著上调，靶向SYK治疗可以明显降低MYC表达。因此推测肝细胞SYK/MYC通路在肝癌发生过程中发挥重要作用。本项目拟通过小鼠原代肝细胞分离培养基础上的SYK基因表达干预，明确SYK对MYC表达的调控作用及相关机制；通过化学诱导的鼠肝纤维化/肝癌模型和基于Cre-LoxP系统的肝细胞SYK条件敲除小鼠，确证靶向SYK对肝癌发生的影响及其临床应用价值，从而为肝癌防治寻找新的治疗靶点。

Early intervention is very important to prevent Hepatocellular carcinoma (HCC). Our previous studies found that tyrosine kinase SYK was significantly up-regulated in chemo-induced rodent fibrotic liver tissues and human fibrotic liver tissues caused by HBV/HCV infection, non-alcoholic steatohepatitis (NASH), alcoholic hepatitis and other causes. Moreover, SYK targeting therapy significantly relieved liver fibrosis/cirrhosis and reduced HCC formation in DEN induced rat or carbon tetrachloride induced mouse liver fibrosis/HCC model. Furthermore, RNA-Seq of primary mouse hepatocytes suggested a significantly increased expression of MYC oncogene accompanied with the up-regulation of SYK expression in hepatocytes isolated form fibrotic mouse liver, while SYK targeting therapy significantly reduced MYC expression in hepatocytes of liver fibrosis mouse. Thus, we hypothesize that SYK/MYC pathway plays key role in hepatocarcinogenesis. This project expresses or interferes SYK in mouse primary hepatocyte to demonstrate SYK increases MYC expression in hepatocytes, uses chemically induced rodent liver fibrosis/HCC model and hepatocytes specific SYK knockout mouse to confirm the clinical application value of targeting SYK/MYC pathway in HCC prevention. The purpose of this project is to find new therapeutic target for HCC prevention and treatment.