项目名称: 泛素连接酶CHIP通过miR-92b/PTEN调控胶质瘤恶性增殖的机制研究
项目编号: No.81472354
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: 徐涛
作者单位: 中国人民解放军第二军医大学
项目金额: 52万元
中文摘要: 脑胶质瘤是颅内最常见的恶性肿瘤,其侵袭性增殖复发是致死的主要原因。因此,探寻胶质瘤恶性增殖的机制具有十分重要的意义。课题组前期研究发现,泛素连接酶CHIP在肿瘤中表达异常增高,体内外研究发现CHIP与细胞增殖能力相关;结合microRNA芯片分析发现,CHIP可调控microRNA-92b表达。同时,我们利用肿瘤信号蛋白芯片筛选发现CHIP过表达后,PI3K-Akt/FOXO 通路异常活化。为了分析其作用机制,我们通过双荧光素报告实验及western blot验证PTEN是miR-92b的靶基因,能够特异性结合PI3K,是PI3K-Akt通路的关键调控分子,因此本研究拟通过分子,细胞,动物实验以及临床组织标本水平验证CHIP通过miR-92b作用其靶基因PTEN调控下游PI3K-Akt/FOXO1通路在胶质瘤恶性增殖行为中的机制研究,以期为恶性胶质瘤临床治疗提供新靶点。
中文关键词: C15_脑;中枢神经系统肿瘤;miRNA;增殖;胶质瘤
英文摘要: Glioma is the most common malignant tumor in CNS.The primary reason of glioma causing death is tumor proliferation.So it is very important to explore the new mechanism.Our previous experiments have shown that CHIP was abnormal expressed in gliomas.At the same time,microRNA-92b expression increased abnormally in gliomas by microRNA array analysis,and Luciferase Reporter Assay have shown that PTEN was a target of microRNA-92b.In addition ,the tumor signal protein chip analysis have shown that the pathway of PI3K-Akt/FOXO were abnormally activated. PTEN can inactivate PI3K .And the pathways of PI3K-Akt/FOXO are downstream signaling pathways.In this experiment ,we will verify the CHIP regulate the target PTEN and the downstream pathways of PI3K-Akt/FOXO through microRNA-92b at the levels of molecule,cell,animal and histopathology.Our research project aims to establish that CHIP can be used as a therapertic target for invasive maligant glioma,and to provide a theoretical basis for developing a novel therapy in the human glioma and improve the clinical treatment effect.
英文关键词: CNS tumor;miRNA;proliferation;Glioma