miR-612调控胶质母细胞瘤对替莫唑胺敏感性的实验研究

Glioblastoma is the most common malignant tumor in central nervous system. Chemotherapy is an important part of comprehensive treatment. Temozolomide is the first choice of clinical chemotherapy drugs for glioblastoma, but resistance is one of the important factors leading to poor clinical outcome. In our previous study, we found that miR-612 is related to the clinical prognosis of glioblastoma patients, but the mechanism remains unknown. Clinical observations show that high expression of miR - 612 favored temozolomide resistance. So whether upregulation of miR - 612 expression mediated temozolomide resistance leading to poor clinical outcome is worth further study. In this research, we are going to collect glioblastoma tissue samples during operation, to analysis miR-612 and the relationship between the chemosensitivity and prognosis;Then through the dual luciferase carrier system to verify the effect of miR-612 target genes; Then using clinical tumor specimens, glioblastoma cells in vitro culture and in situ tumor animal models, to verify the effect of miR-612 regulation of glioblastoma chemosensitivity to temozolomide and its internal mechanism. Taken together, the results from this research will throw light on the treatment of temozolomide-resistant glioblastoma.

胶质母细胞瘤是中枢神经系统最常见的恶性肿瘤，化疗是综合治疗的重要组成部分。替莫唑胺是目前首选化疗药物，然而耐药是导致临床疗效不佳的重要因素。在前期工作中，我们发现miR-612表达与患者临床预后密切相关，但具体机制不明。临床观察结果显示miR-612高表达患者倾向于对替莫唑胺耐药。因此是否存在miR-612表达上调介导替莫唑胺耐药引起临床疗效不佳值得深入研究。本课题拟首先收集胶质母细胞瘤手术组织标本及临床资料，分析miR-612与替莫唑胺化疗敏感性及预后之间的关系；接下来通过双荧光素酶载体系统验证miR-612的作用靶基因；然后在临床肿瘤标本、体外胶质母细胞瘤细胞系及原位肿瘤动物模型中，多方面研究miR-612对肿瘤替莫唑胺敏感性的作用及其内在机制。本课题的研究结果将为临床治疗对替莫唑胺耐药的胶质母细胞瘤提供新的思路和方法。