基于"HCV core-ZEB相互作用促进EMT"探讨HCV感染相关性肝癌的发生机制

Hepatitis C virus (HCV) core protein has been strongly implicated in the progression of HCV infection-associated hepatocellular carcinoma, but its molecular mechanisms has not been clearly elucidated. It has recently become clear that epithelial-mesenchymal transition (EMT) plays an important role in cancer progression and metastasis. As a key transcription factor, zinc finger E-box-binding protein (ZEB) can down-regulate E-cadherin expression and promote tumor EMT process. According to our preliminary data, HCV core suppress expression of E-cadherin via interaction with ZEB. we hypothesize that HCV core protein may promote EMT through direct interaction with ZEB or up-regulate the expression of ZEB. In this project, tissue microarray, phage surface display, ChIP assay, laser confocal imaging and nude-mice transplanted tumor models will be used and the data from the molecular, cellular and animal studies may help understand the interaction of virus and host, and benefit to discover new strategy for HCC therapy.

丙型肝炎病毒（HCV）核心蛋白可能在HCV感染相关性肝癌发生发展中发挥重要作用，但具体机制尚未阐明。上皮间质转化（EMT）是肿瘤发生发展的重要机制，E盒结合锌指蛋白(ZEB)作为EMT关键的调控分子，可通过下调E-cadherin等靶基因表达而促进EMT发生。我们在前期实验中新发现：HCV core可与ZEB相结合，过表达HCV core上调ZEB可抑制E-cadherin表达。由此推测：HCV core可能通过与ZEB相互作用或是上调后者表达来影响E-cadherin水平从而诱导EMT最终促进肝癌发生。本项目拟通过组织芯片、噬菌体表面展示、CHIP、激光共聚焦、裸鼠移植瘤模型等手段，在分子、细胞及动物体三个水平探讨ZEB在HCV core促EMT致肝癌中的详细机制及其对肿瘤细胞转移侵袭等特性的影响，为深入理解病毒与宿主的相互作用和寻找肝癌转移防治新策略提供理论依据。