ZNF143靶向调控MEX3C促进肝细胞癌转移的作用及机制研究

转移是导致肝细胞癌治疗失败和患者死亡的重要原因。上皮间质转化是促使肝细胞癌转移的重要驱动因素。申请人前期研究结果显示ZNF143可以转录激活MEX3C的表达并具有促进肝细胞癌细胞迁移和侵袭的功能。本项目拟从以下三个方面开展研究：1）揭示ZNF143/MEX3C调控轴在肝细胞癌转移中所发挥的作用，2）阐明ZNF143/MEX3C调控轴是否可以通过调控上皮间质转化及其具体作用机制促进肝细胞癌细胞转移，3）初步探讨雷公藤甲素靶向ZNF143/MEX3C调控轴在肝细胞癌中的治疗策略。本研究将为阐明ZNF143/MEX3C调控轴在肝细胞癌转移机制提供重要的理论基础，靶向ZNF143/MEX3C调控轴的治疗策略对肝细胞癌的诊治也具有非常重要的临床意义。

Hepatocellular carcinoma (HCC) is highly aggressive carcinoma that are often fatal due to high level of tumor metastasis. Epithelial–mesenchymal transition (EMT) encompasses dynamic changes from epithelial to mesenchymal phenotypes, which leads to functional changes in cellular metastasis. Previously, we have studied that ZNF143 may activate MEX3C to promotes HCC cell migration and invasion in vitro. Our project is intend to: 1）elucidate the effects of ZNF143 /MEX3C signaling axis on the metastasis of HCC; 2）clarify whether the ZNF143/MEX3C regulatory axis can promote HCC metastasis by promoting EMT and its specific mechanism; 3）preliminarily explore the therapeutic strategy of triptolide (TPL) targeting the ZNF143/MEX3C regulatory axis in HCC. Our study will provide important theoretical basis for elucidating the mechanism of ZNF143/MEX3C regulation axis in HCC metastasis. The treatment strategies of targeting ZNF143/MEX3C regulation axis is also of great significance for the diagnosis and treatment of HCC.