NRG1基因在甲状腺乳头状癌发病中的负向调控作用及其机制研究

项目名称： NRG1基因在甲状腺乳头状癌发病中的负向调控作用及其机制研究

项目编号： No.81502317

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： 魏文俊

作者单位： 复旦大学

项目金额： 18万元

中文摘要： 甲状腺乳头状癌（PTC）是最常见的甲状腺恶性肿瘤，其发病分子机制尚有待研究。Neuregulin-1(NRG1)是一类信号蛋白，主要作为ErbB受体家族的配体发挥功能，参与多条分子信号通路。近来研究显示NRG1分子在恶性肿瘤发病中具有重要的调控作用。课题组前期的研究发现NRG1在甲状腺组织中的表达水平与PTC易感位点8p12相关，NRG1低表达对应较高的PTC发病风险，因此其可能为PTC重要易感基因之一。更重要的是，对比癌旁正常组织，其在PTC组织中亦表现为明显下调，并且该结果独立于BRAF突变存在，提示其可能以独特的负向调控作用参与PTC发病。本项目将在此基础上，深入研究NRG1在PTC中的作用模式和具体分子通路，以及易感位点影响其表达的具体机制。阐明以上问题，将有助于完善对PTC发病分子机制的认识，并为NRG1在恶性肿瘤领域方面的研究提供新思路和新证据。

中文关键词： 甲状腺和甲状旁腺肿瘤；甲状腺乳头状癌；全基因组关联研究；NRG1；负向调控

英文摘要： Papillary thyroid cancer is the most common malignant thyroid tumor and its molecular mechanism remains unclear. Neuregulin-1(NRG1) is a signaling protein, functioning as a ligand of ErbB receptor family and participating in multiple molecular signaling pathways. Recent studies have shown the important role in the initiation of various cancers. Our preliminary studies have demonstrated that NRG1 may be one of susceptibility genes of PTC, and, in thyroid tissue, the expression level of NRG1 was associated with a susceptibility locus detected by genome-wide-association studies. More importantly, compared with normal tissues, NRG1 was down-regulated in PTC tissues, independent of the BRAF mutation status, suggesting some kind of negative regulatory role in PTC. Based on previous works, we will conduct further investigations into the molecular pathway through which NRG1 regulates PTC tumorigenesis, and involved in PTC susceptibility. We believe the implementation of this project will help to understand the molecular mechanism of carcinogenesis of PTC as well as provide clues and evidence for NRG1 studying in malignant tumors.

英文关键词： Thyroid/Parathyroid tumor;Papillary thyroid cancer;GWAS;Neugregulin-1;Negative regulation