miR-29a调控鼻咽癌上皮间质转化(EMT)发生的分子机制及临床意义

项目名称： miR-29a调控鼻咽癌上皮间质转化(EMT)发生的分子机制及临床意义

项目编号： No.81472522

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 邵建永

作者单位： 中山大学

项目金额： 70万元

中文摘要： 高发区鼻咽癌绝大多数为未分化型癌，恶性程度高，放疗后局部控制率低和远处转移率高。本课题组发现鼻咽癌组织存在上皮间质转化（EMT）现象且EMT标志物表达升高与患者预后不良显著相关，我们还在鼻咽癌miRNA差异表达谱分析中发现与肿瘤EMT密切相关的miR-29a在血浆和组织中表达水平均显著下降。本项目拟进一步在体内、外观察过表达或沉默miR-29a对鼻咽癌生物学行为和EMT现象的影响；分析基因变异、甲基化、酶活性对miR-29a低表达的影响；采用基因芯片、定量PCR、荧光素酶报告系统筛选和鉴定miR-29a靶基因，进一步分析靶基因介导的信号通路及其对EMT调控作用；最后分析miR-29a及其靶基因与鼻咽癌EMT分子标志物、临床病理特征和患者预后的相关性，从而阐明miR-29a调控鼻咽癌EMT的分子机制和临床意义，为高发区鼻咽癌分子分型、个体化诊治提供新的标志物或靶点。

中文关键词： 鼻咽癌；miR-29a；间质上皮转化；分子机制

英文摘要： Nasopharyngeal carcinoma (NPC) in endemic areas are frequently found to be undifferentiated subtype with significant malignancy featured by a low rate of local tumor control and a relatively high rate of metastasis. Our preliminary study found that epithelial mesenchymal transition (EMT) phenomenon existed in NPC tissues, and EMT-associated biomarkers were significantly associated with poor prognosis of NPC patients. Moreover, in the analysis of microRNA (miRNA) profiling in NPC, we found miR-29a closely related to the EMT phenomenon was significantly down-regulated in both plasma and tissue of NPC patients, which also demonstrated a postive association with poor prognosis of NPC patients. In the present programme, we will investigate the role of up- or down- regulated expression of miR-29a in modulating the biological behaviors and the EMT phenomenom in vivo and in vitro; explore the influence of genetic variation, methylation and enzymatic activity on downregulating miR-29a expression; screen and validate the target genes of miR-29a by employing the techniques of gene chip, quantitative PCR and luciferase assay; explore associated signal pathways mediated by miR-29a target genes; and finally analyze the association of miR-29a and its target genes with EMT biomarkers, clinical pathological parameters and patient's prognosis. Better understanding in the molecular mechanisms and clinical significance of miR-20a regulating the EMT during the NPC develoment will undoubtedly provide us with new biomarkers or targets for NPC molecular classificaiton and personalized diagnosis and treatment in endemic areas.

英文关键词： Nasopharyngeal carcinoma;miR-29a;Epithelial mesenchymal transition;Molecular mechanism