转录因子Snail乙酰化修饰在肝癌EMT过程中的作用及其调控机制

项目名称： 转录因子Snail乙酰化修饰在肝癌EMT过程中的作用及其调控机制

项目编号： No.81502104

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 江冠民

作者单位： 中南大学

项目金额： 18万元

中文摘要： 肝癌是常见的恶性肿瘤，由于极易出现侵袭与转移，因此病死率非常高。肝癌上皮间质化（EMT）是驱使肝癌细胞侵袭与转移的原动力，最近研究表明EMT关键转录因子Snail在肝癌EMT过程中持续处于高乙酰化状态，Snail乙酰化后可抑制其泛素化降解并显著上调其转录活性，提示Snail的乙酰化修饰在肝癌EMT过程中起着关键作用。因此本课题拟在前期研究基础上，鉴定转录因子Snail乙酰化修饰位点及相关乙酰化酶，确证受乙酰化修饰调控的Snail泛素化位点和肝癌EMT过程中的信号通路蛋白，解析肝癌EMT过程中调控Snail翻译后修饰的相关分子事件，揭示Snail乙酰化-泛素化相互作用在肝癌EMT中作用，并探讨靶向抑制Snail乙酰化对肝癌EMT的影响，从而阐明Snail乙酰化修饰参与调控肝癌EMT的作用及其分子机制，以期为肝癌的防治提供重要的研究基础。

中文关键词： 肝和肝内胆管肿瘤；上皮间质化；乙酰化；泛素化；侵袭与转移

英文摘要： Hepatic carcinoma is a common malignancy, the fatality rate of this carcinoma is very high because it is very easily and earlier generate invasion and metastasis. Recent studies indicate that epithelial-mesenchymal transition(EMT) is the driving force of invasion and metastasis for hepatic carcinoma cells, during the process of EMT in hepatic carcinoma, the transcription factor Snail is at a high acetylation status persistently, the acetylation of Snail inhibits its ubiquitination and significantly raised its transcriptional activity, which indicating that acetylation of snail plays a key regulatory role in EMT of hepatic carcinoma. Therefore, on the basis of our previous research, the major objectives of the present proposal are to identify acetylation modification sites and related deacetylase of transcription factors snail. Furthermore, we will also identify the snail ubiquitination sites and the signaling pathway proteins which regulating the EMT of hepatic carcinoma regulated by acetylation of Snail, demonstrating the molecular events of EMT which regulated by post-translational modifications of Snail in hepatic carcinoma cells, revealing the role of snail that regulated by acetylation-ubiquitination to induction of EMT in hepatic carcinoma and to explore the influence on EMT in hepatic carcinoma by targeting inhibition of Snail, in which we propose to elucidate the key role and molecular mechanism of transcription factors snail acetylation in regulating the EMT of hepatic carcinoma, ultimately provides important foundation for prevention and treatment of hepatic carcinoma.

英文关键词： Liver and intrahepatic bile duct cancer;Epithelial-mesenchymal transition;Acetylation;Ubiquitination;Invasion and metastasis