PinX1基因通过c-Myc抑制胶质瘤增殖的分子机制研究

项目名称： PinX1基因通过c-Myc抑制胶质瘤增殖的分子机制研究

项目编号： No.81502160

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 梅鹏金

作者单位： 徐州医科大学

项目金额： 18万元

中文摘要： 我们既往研究证实PinX1作为一种抑癌基因参与了胶质瘤的发生与发展过程。但如何实现这一作用的具体机制不详。申请者前期研究发现，沉默胶质瘤细胞PinX1基因，显著增加c-Myc和Cyclin D1表达，促进胶质瘤细胞增殖。生物信息分析发现c-Myc核心启动子区域内存在3个潜在的PinX1结合位点。由此，我们提出：PinX1通过与c-Myc启动子结合抑制c-Myc转录，进而影响Cyclin D1表达，抑制胶质瘤增殖。.本研究拟在分子水平，通过双荧光素酶实验、ChIP实验、启动子点突变以及EMSA实验，确认PinX1与c-Myc启动子结合位点，以及对其转录的影响；然后在动物模型上研究PinX1通过c-Myc/Cyclin D1对胶质瘤细胞生长的影响；最后通过胶质瘤组织芯片分析PinX1和c-Myc、Cyclin D1表达之间的关系，以及与临床病理和预后的关系。为寻找胶质瘤新的治疗靶点提供理论依据

中文关键词： 胶质瘤；增殖；PinX1；c-Myc；Cyclin；D1

英文摘要： In our previous study, we identified that PinX1 as a tumor suppressor gene involved in glioma development process. However, the underlying molecular mechanism is not clear. In our preliminary experiment, we found that silencing PinX1 gene can increase c-Myc and Cyclin D1 expression in glioma cells, and the cells proliferation ability is also increasing. The biological information software predicted that there were three potential PinX1 binding sites in the c-Myc promoter. Consequently, we suppose that PinX1 regulate glioma proliferation through inhibiting c-Myc transcriptional expression and Cyclin D1 expression by binging with c-Myc promoter..To confirm this hypothesis, we will investigate the effect of PinX1 on c-Myc transcriptional expression, and verify the binding sites in the c-Myc promoter by EMSA, ChIP and site mutation. Then, we will verify if PinX1 can suppress glioma grow through c-Myc/Cyclin D1 signal pathway by in vivo nude moues model. Lastly, we will analysis the correlation between the PinX1, c-Myc, Cyclin D1 and the pathology, and prognosis of glioma patients by tissue microarray.Our study will provide evidence for new therapeutic target for glioma.

英文关键词： glioma;proliferation;PinX1;c-Myc;Cyclin D1