核因子NF90在肝癌细胞中稳定细胞周期蛋白Cyclin E1 mRNA的机制研究

项目名称： 核因子NF90在肝癌细胞中稳定细胞周期蛋白Cyclin E1 mRNA的机制研究

项目编号： No.81502394

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： 蒋维

作者单位： 复旦大学

项目金额： 18万元

中文摘要： 肝癌是我国高发的恶性肿瘤之一，而周期蛋白Cyclin E1的高表达与肿瘤恶性转化相关。申请人的前期研究报道了一个在肝癌组织中显著上调表达的NF90蛋白，通过与Cyclin E1 mRNA结合，调控其稳定性并增加Cyclin E1的蛋白表达，从而促进肝癌细胞的恶性增殖。但是NF90的上游调控信号通路并未阐明。我们的后续研究发现NF90选择性地与CDK2互作，382位丝氨酸可能是CDK2的磷酸化位点。该位点的突变影响Cyclin E1蛋白表达，并调节肝癌细胞周期进程。本项目将在前期研究基础上，深入揭示CDK2对NF90的调控机制，综合探讨NF90作为肝癌分子标志物和个性化治疗靶标的可行性。

中文关键词： 肝癌；肿瘤发生；NF90；CDK2；磷酸化

英文摘要： Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. There is a correlation between the overexpression of Cyclin E1 and the malignant transformation of the tumor. In the previous study, we reported that NF90 was significantly upregulated in HCC specimens. By directly binding to Cyclin E1 mRNA, NF90 modulated its stabilization and increased the expression of Cyclin E1 protein, which further aggravated HCC cell proliferation. However, upstream signaling pathway of NF90 remains unknown. Our recent study demonstrates that NF90 can co-immunoprecipitate specifically with CDK2 and Ser382 of NF90 may be a site phosphorylated by CDK2. Mutation of Ser382 can regulate the expression of cyclin E1 and affect the HCC cell cycle progression. This proposal will focus on understanding the mechanism of the regulation of NF90 by CDK2 through phosphorylation, and exploring the possible application of NF90 as a biomarker and therypeutic target for HCC.

英文关键词： Hepatocellular carcinoma;Tumorigenesis;NF90;CDK2;Phosphorylation