基于定量磷酸化蛋白质组学的脯氨酰顺反异构酶Pin1介导肝癌发生的关键信号通路的筛选

项目名称： 基于定量磷酸化蛋白质组学的脯氨酰顺反异构酶Pin1介导肝癌发生的关键信号通路的筛选

项目编号： No.81502115

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： 杨达云

作者单位： 福建医科大学

项目金额： 16万元

中文摘要： 肝癌是一种世界范围内的主要恶性肿瘤，具有高致死率。目前迫切需要对肝癌的发生机制进行深入研究，以探索新的治疗靶点。脯氨酰顺反异构酶Pin1是一种新型的后磷酸化信号调节者，它能够对控制细胞增殖和转化的多条信号通路进行调节。Pin1在肝癌中过表达，对肝癌发生起重要作用，但是Pin1介导肝癌发生的途径不清楚。本课题采用定量磷酸化蛋白质组学、生物信息学分析和一系列生物学方法，从细胞和动物两个层面筛选出并确定Pin1介导肝癌发生的关键信号通路。内容包括：1）通过定量磷酸化蛋白质组学获知Pin1敲减的肝癌细胞和Pin1转基因小鼠肝组织的磷酸化蛋白质和磷酸化位点数据；2）通过生物信息学分析筛选出受Pin1调节的重要信号通路；3）运用一系列生物学实验对重要信号通路在肝癌发生中的介导作用进行验证；4）综合所有实验结果，揭示Pin1介导肝癌发生的关键信号通路及其作用机制。

中文关键词： 肝癌；Pin1；信号通路；定量磷酸化蛋白质组学；生物信息学

英文摘要： Hepatocellular carcinoma (HCC) is one of the leading worldwide cancers with high mortality. It is urgent need to further study the molecular mechanism of development of HCC to explore new therapeutic targets. Pin1 is a novel postphosphorylation signaling regulator, which regulates many signaling pathways controlling cell proliferation and transformation. Pin1 is overexpressed in HCC and contributes to hepatocarcinogenesis. However, the molecular mechanism for mediation of Pin1 to hepatocarcinogenesis is largely unclear. The aim of this project is to screen out and validate the key signaling pathways for mediation of Pin1 to hepatocarcinogenesis at two levels, including cell and animal model, by quantitative phosphoproteomics, bioinformatics analysis combined with a series of biological methods. The research contents are as follows: 1) Obtain the phosphorylated proteins and phosphorylation sites in Pin1 knockdown HCC cells and in liver tissue of Pin1 transgenic mice via quantitative phosphoproteomics; 2) Screen out the key signaling pathways regulated by Pin1 with bioinformatics analysis; 3) Verify the role of these key signaling pathways in hepatocarcinogenesis by a series of biological methods; 4) Integrate all the experimental results to reveal the key signaling pathways for mediation of Pin1 to hepatocarcinogenesis.

英文关键词： liver cancer;Pin1;signaling pathway;quantitative phosphoproteomics;bioinformatics