PDE4DIP影响结直肠癌形成的分子机制研究

项目名称： PDE4DIP影响结直肠癌形成的分子机制研究

项目编号： No.81472556

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： 廖婉琴

作者单位： 温州医科大学

项目金额： 72万元

中文摘要： 结直肠癌(Colorectal cancer,CRC)是常见的消化道恶性肿瘤。目前研究认为结直肠癌的发生是多种癌基因表达异常或抑癌基因表达失活所致。PDE4DIP是一个全新的微管调节蛋白，参与微管装配与动态平衡调控。转座子分析显示PDE4DIP是一个潜在的小鼠肠癌调控基因。我们前期研究发现PDE4DIP在结直肠癌细胞、组织中低表达，过表达PDE4DIP显著抑制结直肠癌细胞的增殖和肿瘤形成，提示PDE4DIP在结直肠癌中可能是一个抑癌基因。在此基础上，本项目拟结合分子、细胞生物学和动物模型等技术手段进一步检测PDE4DIP在结直肠癌形成中所起的作用，探索PDE4DIP调控的关键靶基因、相关信号途径并进而阐明PDE4DIP调控结直肠癌形成的分子机制。研究结果有望为结直肠癌的治疗和研究提供新的分子靶点和途径。

中文关键词： PDE4DIP；结直肠癌；细胞增殖；肿瘤形成；分子机制

英文摘要： Colorectal cancer (CRC) is the most common cancer of the gastrointestinal tract. A number of key oncogenes, tumour suppressor genes and pathways have been implicated in colorectal tumorigenesis. PDE4DIP is a novel microtubule regulator, that regulates microtubule assembly and dynamics. In a transposon-based genetic screen in mice, the PDE4IP gene was identified as a CRC driver gene. Our primary results showed that PDE4DIP was down-regulated in human CRC cells and the majority of tumor samples. Moreover, overexpression of PDE4DIP significantly supressed CRC cell proliferation in vitro and tumorigenesis in vivo. Together, these results suggest that PDE4DIP is a potential tumor suppressor in CRC. On the basis of our primary findings, in this study, we aim to explore the function of PDE4DIP in CRC. We will also try to identify the PDE4DIP-target genes, as well as the PDE4DIP-mediated cell signaling pathways in CRC. The findings of this study will reveal the molecular mechanisms underlysing PDE4DIP involved in colorectal tumorigenesis, and might provide novel targets for CRC therapy.

英文关键词： PDE4DIP;colorectal cancer;cell proliferation;tumorigenesis;molecular mechanisms