PEDF促进肝细胞癌转移的功能及分子机制研究

色素上皮衍生因子（PEDF）与肿瘤血管新生、肿瘤生长和转移有着密切的关系，国内外研究表明PEDF在不同肿瘤中起到复杂甚至相矛盾的功能，而其作用机理尚未阐明，PEDF在肝细胞癌转移中的功能及机制迄今未见报道。我们前期研究发现，与配对癌旁肝组织相比，PEDF在人原发性肝细胞癌组织中明显高表达且与患者肝内转移相关；体外过表达PEDF能够促进肝细胞癌细胞迁移和侵袭；mRNA测序分析结果表明PEDF能够调控肿瘤转移相关信号通路。.基于上述初步研究，本项目拟在细胞、动物模型和临床病例三个层面进一步阐述PEDF在肝细胞癌中的功能及表达调控机制。采用mRNA测序、免疫共沉淀、质谱技术、信号通路磷酸化芯片和ChIP等技术，结合生物信息学分析，筛选PEDF及其受体所参与的信号通路及其表达调控机制，深入探讨PEDF影响肝细胞癌转移的分子机制，以期为肝癌的有效治疗、预防复发转移及预后提供可靠的实验依据和理论指导。

Pigment epithelium-derived factor (PEDF) plays complex and often contradictory roles in cancer angiogenesis, tumor growth and metastasis. And the role of PEDF in the metastasis of human primary hepatocellular carcinoma （HCC） remains unclear. In our previous study, we found PEDF acts as an important regulator in the metastasis of HCC. The expression of PEDF is higher in HCC tissues, compared to matched non-cancerous liver tissues, and correlates intrahepatic metastasis. Transwell assays showed overexpression of PEDF significantly increased migration and invasion of HCC cells and mRNA sequence analysis showed that PEDF can regulate metastasis related pathway. It means that PEDF plays very important roles in HCC progression. .In the present project, we will further explore the function of PEDF on HCC progression using more cell lines by overexpression and knockdown of PEDF, especially in vivo experiments. Further, with bioinformatics analysis, we want to identify the receptor, the target gene, the pathway that PEDF involved in and the transcription factor which regulates PEDF expression using mRNA sequence, co-immunoprecipitation (Co-IP), Liquid chromatography–mass spectrometry (LC-MS), Phospho Explorer Assay, and ChIP assays. This project will expound the function and mechanism of PEDF on metastasis of HCC and provide the necessary experimental basis and the correct guidance to effective treatment, prevention of recurrence and metastasis as well as the prognosis of HCC.