miRNA-422a通过靶向调控PI3K-Akt信号通路抑制神经胶质瘤增殖、侵袭及转移

项目名称： miRNA-422a通过靶向调控PI3K-Akt信号通路抑制神经胶质瘤增殖、侵袭及转移

项目编号： No.81502183

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： 王仁杰

作者单位： 中国人民武装警察部队后勤学院

项目金额： 18万元

中文摘要： 研究表明microRNA（miRNA）分子通过调控癌基因、抑癌基因及重要细胞信号通路参与神经胶质瘤的增殖、侵袭和转移。本项目前期研究发现miR-422a分子在神经胶质瘤中低表达；过表达miR-422a诱导神经胶质瘤细胞周期阻滞和凋亡，从而抑制增殖；同时过表达miR-422a抑制神经胶质瘤细胞的体外侵袭和转移能力；此外课题组基于cDNA芯片和生物信息学技术，明确了miR-422a下游靶基因包含有PI3K-Akt信号通路的四个关键分子。上述结果提示miR-422a与神经胶质瘤的增殖、侵袭和转移密切相关，并且提示miR-422a通过PI3K-Akt信号通路参与调控神经胶质瘤的发生发展。本课题组拟进一步确认其直接靶基因，进行功能分析，并研究miR-422a的上游调控机制。通过本研究，将有助于为以miRNA为靶点设计神经胶质瘤靶向药物提供理论线索和实验依据。

中文关键词： 胶质瘤；微小RNA；PI3K-Akt信号通路；肿瘤细胞增殖；肿瘤细胞转移

英文摘要： Studies reported that microRNA (miRNA) molecules take part in the process of Glioma cell proliferation, invasion and metastasis by regulate oncogenes, tumor suppressor genes and important cell signal transduction pathways. Our previous research showed the low expression of miR-422a molecules in glioma by using RT-PCR and Northern Blot technologies; overexpression of miR-422a suppressed the glioma cell proliferation, induce apoptosis and block cell cycle; meanwhile, the glioma cell invasion and metastasis capabilities in vitro was been depressed by miR-422a; we also has filtered 4 members of the PI3K-Akt signaling pathway as miR-422a downstream target gene by using cDNA chip and biological information methods. The propose of this study is to further confirm the direct target genes of miR-422a, explore the molecular mechanisms of miR-422a in glioma, and to verify the upstream regulatory mechanism in the process of miR-422a downregulation. This study will deeply explore the upstream and downstream regulation mechanism of miRNA-422a in glioma, and lay a theoretical foundation of deeply understanding of the role of miR-422a in the occurrence and development of glioma.

英文关键词： glioma;microRNA;PI3K-Akt signal pathway;tumor cell proliferation;tumor cell metastasis