microRNA-424及其CpG岛甲基化调节在胶质瘤侵袭机制中的研究

项目名称： microRNA-424及其CpG岛甲基化调节在胶质瘤侵袭机制中的研究

项目编号： No.81472365

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： 吕世军

作者单位： 潍坊医学院

项目金额： 72万元

中文摘要： 脑胶质瘤预后差的重要原因是胶质瘤细胞的脑内高侵袭性。在前一个国家自然基金支持下，我们研究证实：ARK5在胶质瘤侵袭中具有关键作用，其蛋白表达明显促进胶质瘤细胞侵袭；同时，也发现某些胶质瘤细胞内ARK5 mRNA水平升高而蛋白表达降低的现象，这抑制了胶质瘤的侵袭能力。进一步研究发现，在患者胶质瘤组织中miR-424的表达与ARK5的表达呈负相关。经过生物信息学分析和前期预实验结果验证，我们推测：miR-424可能通过靶向抑制ARK5的翻译介导了胶质瘤细胞的侵袭，而胶质瘤细胞通过miR-424启动子区CpG岛的甲基化降低了胶质瘤细胞miR-424的表达。为验证以上假设，本项目拟从分子、细胞和动物整体水平阐明miR-424及其表观遗传修饰在胶质瘤侵袭中的调控机制，为抑制胶质瘤的侵袭和复发提供新的靶标，为胶质瘤的诊断和预后判断提供新的生物学指标。

中文关键词： C15_脑；中枢神经系统肿瘤；侵袭；微小RNA；甲基化修饰

英文摘要： The main reason of the poor prognosis of glioma is its highly invasive ability. Our previous study showed that : ARK5 played an important role in glioma invasion; The ARK5 protein expression and glioma invasion are closely related, whereas the expression of ARK5 mRNA are not consistent with its protein expression. Recently, using the high-throughput sequencing, we showed that miR-424 was significantly reduced in glioblastoma. Our preliminary study also showed that ARK5 protein expression and miR-424 had a negative correlation in glioma cell lines and glioma tissues. Through bioinformatics analysis and preliminary findings validate, we hypothesize that miR-424 may inhibit the translation of ARK5 by targeting ARK5 5'-UTR and miR-424 is reduced by the methylation of its promoter CpG islands. The project intends to clarify the regulatory mechanism of the regulation that miR-424 inhibits ARK5 expression and the epigenetic modifications of miR-424 in glioma invasion. These hypothesis will be verified by cell culturing, protein assay and in vivo research involving animal model. Based on the results from this study, we can provide new diagnostic and prognostic biomarkers for glioma and new target for gene therapy.

英文关键词： glioma;invasion;microRNA;methylation