EBV-LMP1与抑癌基因WWOX失活在鼻咽癌发生中的机制研究

项目名称： EBV-LMP1与抑癌基因WWOX失活在鼻咽癌发生中的机制研究

项目编号： No.81460414

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 莫武宁

作者单位： 广西医科大学

项目金额： 47万元

中文摘要： 广西是全国鼻咽癌（NPC）高发区。本课题前期研究首次发现抑癌基因WWOX在NPC组织中表达降低，且随患者病情进展而逐步下降，并与淋巴结转移相关。其下调的主要原因是由于启动子甲基化所致，但其机制仍未清楚。鼻咽癌与EBV感染密切相关，而EBV可诱导抑癌基因甲基化，本课题拟以EBV的主要致癌基因LMP1为切入点，采用基因转染技术、siRNA沉默技术及差异蛋白质组学分析，研究EBV主要致瘤成分LMP1对WWOX基因启动子甲基化的影响，探讨 EB病毒诱导WWOX失活的机制。进一步研究鼻咽癌LMP1与WWOX相互作用对下游基因的影响，阐明其下游调节网络途径及关键的调控蛋白质分子，为筛选早期诊断的生物标志物、研发新治疗靶标提供新思路。

中文关键词： C03_鼻咽肿瘤；LMP1；WWOX；差异蛋白组学；分子机制

英文摘要： Guangxi is the high-incidence area of nasopharyngeal carcinoma (NPC) throughout the country. Early in our project, we first found the decreased expression level of tumor suppressor gene WWOX in NPC tissue. Furthermore, the lower expression level of WWOX was found along with the NPC progression and was also associated with lymph node metastasis. Althouh we know that it is mainly due to the methylation in promoter of WWOX gene, the down-regulation mechanism is still not clear. As nasopharyngeal carcinoma is closely related to the EBV infection, and the methylation of tumor supressor gene can also be induced by EBV. Therefore, we intend to regard LMP1 (the main oncogene of EBV) as a breakthrough point. The technology of gene transfection, siRNA silencing and differential proteomics analysis are applied to clarify whether LMP1 has influence on gene promoter methylation of WWOX and discuss the mechanism that EBV induces WWOX inactivation. Furthermore, we will study whether the interaction between LMP1 and WWOX has influence on downstream genes to get knowledge of downstream regulation network and key control protein molecules, which contributes to selecting biomarker for eary diagnosis of NPC and providing new idea for development of new therapeutic targets.

英文关键词： Nasopharyngeal carcinoma;latent membrane protein 1;WW domain- containing oxidoreductase;Comparative proteomics;Molecular mechanism