bantam对Dpp信号通路的调节影响神经胶质细胞及前体干细胞的增殖

项目名称： bantam对Dpp信号通路的调节影响神经胶质细胞及前体干细胞的增殖

项目编号： No.31501039

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 李英

作者单位： 重庆医科大学

项目金额： 21万元

中文摘要： 脑胶质瘤是中枢神经系统最常见的恶性肿瘤，了解其发生发展的机制是有效治疗的关键，microRNAs是内源性非编码小RNA，通过负性调节靶基因参与脑胶质瘤的发生发展。本课题组前期研究发现：在生物进化过程中高保守果蝇microRNA bantam是视觉中枢内神经胶质细胞及前体干细胞增殖的重要促进因子；bantam人同源体miRNAs具有相似促进胶质瘤细胞增殖的功能；体内体外实验证实bantam能靶向作用Dpp信号通路的关键信号传递分子Mad。基于此，我们提出科学假设：在中枢神经系统内神经胶质细胞及前体干细胞中，bantam能通过其靶向作用Mad从而负性调节Dpp信号通路的强度，从而调控细胞增殖，并且这种调节在进化上具有保守性，是影响人脑胶质瘤细胞增殖的重要机制。我们将以遗传学与分子细胞生物学相结合的方法，利用果蝇模式生物和人胶质瘤细胞模型开展课题研究，课题结果将为临床治疗胶质瘤提供新的科学依据。

中文关键词： 黑腹果蝇；非编码RNA；信号转导；胶质瘤干细胞；肿瘤发生

英文摘要： Malignant gliomas are the most common malignant tumors that develop in the central nervous system and are essentially incurable. Understanding the biology of the disease is the pivotal way leading to the effective treatment. microRNAs are the newly identified, endogenous, small non-coding RNAs, which participate in developing gliomas by its negative regulation on target genes. Our previous finding shows that evolutionarily conserved microRNA bantam is critical for the proliferation of glial cells and glial precursor cells in Drosophila optic lobe. Human homologs of bantam showed the similar function as bantam that they can stimulate the proliferation of the U87 glioblastoma cells. And Mad, the Dpp signaling transduction molecule, is the target of bantam. Based on these findings, we hypothesize that bantam stimulates the proliferation of glial cells and glial precursor cells through its inhibitory effect on Mad. And this might be the conserved mechanism that affects the proliferation of the human glioblastoma cells. We will use the tools from genetics and molecular and cellular biology to test our hypothesis in both Drosophila animal and the human glioblastoma cell line. Our results will certainly shed light on the new clues to the effective treatment of gliomas.

英文关键词： Drosophila melanogaster;non-coding microRNA;signal transduction;glioblastoma stem cells;tumorigenesis