Smad3在肝癌的发生阶段发挥抑癌的重要作用，我们的前期工作发现 Fli-1与Smad3存在相互作用，并能显著抑制Smad3的转录。更重要的是，在人的肝炎、肝硬化及肝癌的临床样本中Fli-1的表达水平呈递增趋势，初步细胞生物学功能研究发现Fli-1具有促进肝癌细胞增殖的作用。这提示Fli-1可能促进肝癌的发生。本项目拟在此重要线索基础上，通过临床样本分析结合分子生物学手段，于临床水平分析Fli-1与肝癌发生及预后的相关性，于细胞水平检测Fli-1对肝癌细胞生长、周期、凋亡及迁移的影响，于分子水平阐明Fli-1通过抑制Smad3转录进而调控TGF-β/Smad信号转导通路促进肝癌发生的分子机制，并进一步利用致癌剂DEN诱导小鼠发生肝炎-肝癌动物模型，于体内水平研究Fli-1对肝癌发生的影响及分子机制。通过以上努力将可能发现新的肝癌发生调控机制，同时也将为其治疗提供新的潜在靶点。

Smad3 that plays a critical role in tumorigenesis of Hepatocellular Carcinoma (HCC) as a tumor suppressor. Our previous research has revealed that Fli-1 interact with Smad3 and inhibit the transcription of Smad3. More important, the expressive level of Fli-1 is increased in hepatitis, Cirrhosis and HCC tissue. In the study of cell biological function we have found that Fli-1 promotes cell proliferation in HCC cell line. These findings suggest that Fli-1 may promote HCC formation. Thus, this project is to analyze the correlation of Fli-1 and HCC formation and prognosis in clinical level, detect the effect of Fli-1 on cell growth, cycle, apoptosis and migration in cell level, reveal Fli-1 promotes the occurrence of HCC through the TGFβ/Smad signaling pathway by inhibit the transcription of Smad3 in molecular level with the analysis of breast samples and molecular biological methods. Furthermore, we will establish an hepatitis-HCC mice model induced with carcinogens of DEN to investigate the effects and molecular mechanisms of Fli-1 on HCC formation. Through all the above efforts, we might find a new regulation mechanism of HCC and provide a new potential target for HCC treatment.