脑胶质瘤干细胞相关microRNAs功能及其调控机制与临床应用研究

项目名称： 脑胶质瘤干细胞相关microRNAs功能及其调控机制与临床应用研究

项目编号： No.81201994

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 夏洪平

作者单位： 皖南医学院

项目金额： 24万元

中文摘要： 胶质瘤干细胞是导致胶质瘤对放化疗抗拒和术后易复发的关键，寻找调控胶质瘤干细胞关键分子对于开发靶向胶质瘤干细胞治疗具有重要意义。本课题组分别从不同胶质瘤细胞系和组织中获取胶质瘤干细胞，并通过检测其自我更新、多向分化、成瘤能力及干细胞标记物表达鉴定。初步microRNA表达谱及定量PCR分析已锁定一系列胶质瘤干细胞相关microRNAs (如miR-30a, miR-34a, miR-101, miR-124 and miR-200a等) 显著差异表达。本项目将通过转染过表达或抑制胶质瘤干细胞相关microRNAs，深入探究其调控胶质瘤干细胞自我更新与成瘤分子机制及关键靶标；并通过收集胶质瘤病人组织与血液样本，检测相关microRNAs及其靶标表达，结合临床分析其作为诊断标志物的应用前景。本研究将为胶质瘤诊断与治疗提供新型分子标志物和干预靶点，为发展新型靶向胶质瘤干细胞的治疗策略奠定基础。

中文关键词： 胶质瘤；干细胞；微小RNA；CD133；神经球

英文摘要： Glioma stem cells are the key factors which lead to radiotherapy and chemotherapy resistance of malignant glioma. So it is important to investigate the key molecules on regulation of glioma stem cells for the development of the Glioma molecular markers and targeted glioma stem cell therapy. With the development of glioma stem cell separation and identification technique, we obtained glioma stem cells from different glioma cell lines and clinical tissues, and confirmed by detecting their self-renewal, multipotent differentiation, tumorigenicity and stem cell markers. We identified some glioma stem cells of microRNAs (miR-30a, miR-34a, miR-101, miR-124 and miR-200a) by microRNA expression profiling and real-time quantitative PCR analysis. This project will investigate the effects and molecular mechanisms of microRNA on glioma stem cell self-renewal and tumorigenicity by transient or stable overexpression or knockdown. The expression of microRNAs and their targets in glioma patients' tissues and blood will also be analyzed to develop them as diagnostic markers. This study will provide novel molecular markers for diagnosis and targets for treatment of gliomas to develop new strategies on targeting glioma stem cells treatment.

英文关键词： glioma；stem cell；microRNA；CD133；neurosphere