肝细胞癌(HCC)是广西死亡率最高的恶性肿瘤。肝癌发生发展涉及多种蛋白异常表达及相互作用。SMP30 是本课题组发现的新肝癌抗原，在肝癌组织低表达且与肝癌发生发展相关，但机制尚不清楚。我们前期发现DNA甲基化、micoRNA表观遗传调控是SMP30基因沉默的主要方式，生物信息学分析表明SMP30与AFP、PON1、PBLD三个蛋白存在互作关系，而这三个蛋白又与肝癌关系密切并参与MAPK信号通路调节，推测SMP30与这些蛋白相互作用并通过该信号通路调节肝癌发生发展。本课题拟在体外细胞模型和体内裸鼠移植瘤模型上研究SMP30 DNA甲基化及microRNA表观遗传调控对SMP30表达水平影响及其二者的协同作用，观察高表达和沉默SMP30基因对肝癌细胞生物学行为影响，分析验证SMP30与之互作蛋白关系，通过互作基因共表达研究相关MAPK信号通路蛋白的变化，以阐明SMP30在肝癌发生发展中的作用。

Hepatocellular carcinoma (HCC) is first killer of malignant tumor in Guangxi province. The occurrence and development of HCC is relative to abnormal expression of various proteins and their interactions.SMP30 is one of new tumor-associated antigen found in our laboratory.SMP30 had a low expression in HCC tissue with a high expression in adjacent tissues of HCC. However,the regulating mechanism of its expression is not clear. We found that epigenetic regulation,such as DNA methylation and micoRNA, was the mainly way for the gene silence of SMP30. Bioinformatics predict that there is a relationship of protein-protein interaction between SMP30 and the three proteins of AFP, PON1 and PBLD.These three proteins are closely relevant to liver cancer and the regulation of MAPK signaling pathway. We propose that the protein-protein interaction between SMP30 and its relating proteins involving in the development of HCC by the role of signaling pathways. This project aims to study the effect of epigenetic regulation of DNA methylation and microRNA on SMP30 expression levels by the model of cell in vitro and nude mice in vivo, to research the coordination effect of methylation and microRNA. We are making further research the role of overexpressing and silencing SMP30 gene on cell biological behavior and eluciate the relationship of HCC occurrence, development and protein interaction of SMP30 with the change of protein level in MAPK signal pathway.