GAS5通过调控miR-18a-5p对神经胶质瘤生物学行为的影响及机制研究

项目名称： GAS5通过调控miR-18a-5p对神经胶质瘤生物学行为的影响及机制研究

项目编号： No.81502161

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： 刘茜

作者单位： 重庆医科大学

项目金额： 18万元

中文摘要： 神经胶质瘤是最常见的原发性颅内肿瘤，临床治疗效果欠佳，因此，找到胶质瘤形成和发展中的关键分子，将为胶质瘤的治疗提供新的靶点。近年来研究发现，长非编码RNA（long noncoding RNA, lncRNA）在肿瘤中发挥重要作用，但鲜有文献报道lncRNA在胶质瘤中发挥的功能。课题组前期工作发现，过表达lncRNA GAS5可以抑制胶质瘤细胞的增殖，迁移和侵袭能力，并可降低miR-18a-5p的表达。文献证实，miR-18a-5p通过抑制其靶基因的表达以增强胶质瘤细胞的增殖、迁移和侵袭能力。因此，推测GAS5可能通过降低miR-18a-5p的表达，进而减弱miR-18a-5p对靶基因的抑制作用，从而影响胶质瘤的生物学行为。本课题组拟用细胞生物学和分子生物学方法，从离体和在体两方面，研究GAS5通过调控miR-18a-5p对胶质瘤生物学行为的影响和机制，为临床确定新的治疗靶点提供实验基础。

中文关键词： 胶质瘤；非编码RNA

英文摘要： Glioma is the most common brain tumor in humans. Patients with malignant glioma typically fail to respond to medical treatments. Discovery of a key gene related to the initiation and progression of glioma will identify therapeutic targets for glioma treatment. Emerging evidence reveals that long noncoding RNA(lncRNA) play an important role in tumor. A few studies revealed the function of lncRNA in glioma. Our preliminary studies showed that overexpression of lncRNA GAS5 in U251 cells significantly downregulated miR-18a-5p, and suppressed cell proliferation, migration and invasion. miR-18a-5p has been proved to promote glioma cell proliferation, migration and invasion through regulating the target gene. Therefore, we hypothesize GAS5 plays a key role in biological character of human glioma cells through regulating miR-18a-5p. To test our hypothesis, we propose to study the role of GAS5 in cell growth, cell cycle, apoptosis, migration and invasion of human glioma cells and underlying mechanism. The success of this project will provide new sight into molecular mechanisms of GAS5 in human glioma and facilitate the identification of novel therapeutic targets for clinical applications.

英文关键词： glioma;long noncoding RNA