应用“睡美人”转座子、CRISPR/Cas9 系统研究肝细胞癌典型 WNT 信号通路涉及的抑癌基因

原发性肝癌(hepatocellular carcinoma, HCC)简称肝癌，是指在肝细胞或肝内胆管上皮细胞发生的恶性肿瘤，居我国癌症死因的第2位。引发肝癌因素很多，如各种原因引起的肝硬化、肝炎病毒引起等，在中国有普遍性，因此探索肝癌的遗传机理以及其引发肝癌的分子机制有重要的社会意义。基因编辑技术是近年热门研究癌症基因的技术，项目拟透过由龚伟强博士开发的“睡美人”转座子及CRISPR/Cas9基因编辑技术，插入特异的质粒及CTNNB1激活基因构建基因编辑小鼠，去籂选有关抑癌基因。并透过研究相关的蛋白及代谢物的变化为抑癌基因在HCC发病上的角色提供新的模式和思路，对HCC的防治都具有重要的理论和现实意义。

Hepatocellular carcinoma or liver cancer is the malignant tumor developed in liver cell or intrahepatic bile duct endothelial cell, it is the second cause of cancer deaths in China. It is clear that there are many cause of liver cancer, including the cirrhosis by various factors or hepatitis. These causes are very common in China, therefore, exploring the genes and molecular mechanism in the liver cancer development is very important to the society. Gene editing technique is a new tool for cancer gene study. In this project, Dr. Vincent Keng use a new gene editing technique developed by his team called "sleeping beauty" transposon system and CRISPR/Cas9 as genetic tools to discover important tumor.suppressor genes involved in mouse liver cancer development. Together with the analysis of the related protein expression, also the changes in the metabolite in the mouse animal model, the data obtained from this research proposal will be paramount in the understanding, treatment and prevention of liver cancer.