长链非编码RNA-H19通过竞争性结合miR-181家族和衍生miR-675双通路调控脑胶质瘤EMT进程的机制研究

项目名称： 长链非编码RNA-H19通过竞争性结合miR-181家族和衍生miR-675双通路调控脑胶质瘤EMT进程的机制研究

项目编号： No.81472362

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： 尤永平

作者单位： 南京医科大学

项目金额： 80万元

中文摘要： EMT（上皮间质转化）在肿瘤细胞侵袭过程中起关键作用。我们前期通过全转录组测序发现：长链非编码RNA-H19与胶质瘤恶性级别、患者预后及EMT进程密切相关。生物信息学分析提示H19上存在miR-181家族潜在结合位点。进一步预实验证实：敲低H19可抑制胶质瘤细胞侵袭并调节EMT经典标志物表达水平，同时可降低miR-181家族潜在靶基因的蛋白表达水平及H19 编码的miR-675表达水平。由此我们推测H19作为miR-181家族分子海绵及miR-675前体实现对胶质瘤EMT进程的调控。本课题拟通过临床大样本分析、RNA结合蛋白免疫沉淀、体内交联等方法明确H19表达的临床意义及竞争性结合miR-181家族和衍生miR-675双通路介导的EMT进程调控，并分析其调控关系对胶质瘤细胞侵袭等恶性表型的影响。课题可构建H19对EMT进程的多重调控网络，在长链非编码RNA作用模式方面进行有益的探索。

中文关键词： C15_脑；中枢神经系统肿瘤；胶质瘤；长链非编码RNA；微小RNA；上皮间质转化

英文摘要： Epithelial-mesenchymal transition (EMT) plays a critical role in cancer cell invasion. In our previous studies, whole transcriptome sequencing was performed and revealed that H19 was associated with malignant progression, clinical prognosis and EMT process in glioma. Bioinformatics predicted miR-181s' binding sites in H19.Preliminary studies indicated that H19 siRNA resulted a decrease of invasion ability and regulated the expression of EMT markers.Downregulation of H19 also decreased miR-181s' potential target genes at protein level and H19 encoded miR-675 expression in glioma cells. Here, we propose a hypothesis that H19 may regulate EMT process via functioning as miR-181s sponge and deriving miR-675. Presently, we aim to validate the functional regulation of H19 on EMT process, the competing regulation of miR-181s' target genes and miR-675 mediated EMT regulation network. In summary, our results may provide novel targets and optimize treatment strategies for molecular targeted therapy in glioma.

英文关键词： brain tumor;glioma;long noncoding RNA;microRNA;EMT