Wnt信号通路主要成员在新疆维吾尔族与汉族胰腺癌干细胞中的表达及其调控机制研究

项目名称： Wnt信号通路主要成员在新疆维吾尔族与汉族胰腺癌干细胞中的表达及其调控机制研究

项目编号： No.81460361

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王喜艳

作者单位： 新疆医科大学

项目金额： 47万元

中文摘要： 最近的观点认为胰腺癌干细胞是胰腺癌恶性生物学行为产生与维持的核心，针对肿瘤干细胞的调控研究也已成为胰腺癌研究领域新的热点。Wnt信号通路是已知与肿瘤干细胞调控关系最为密切的信号通路之一，且最近的研究也报道了其主要成员在胰腺癌组织中的异常表达，然而国内关于胰腺癌干细胞中Wnt信号通路调控作用的研究尚处于起步阶段，相关报道较少。我们前期研究的结果显示，新疆维吾尔族与汉族胰腺癌组织中Wnt通路部分成员的表达存在差异，这种差异是否同样存在与不同民族的胰腺癌干细胞中？其调控机制如何？为回答上述问题，本项目拟通过不同民族胰腺癌干细胞表达谱差异分析、mRNA与蛋白定量检测及基因过表达与表达阻遏等方法，筛选出胰腺癌干细胞相关的Wnt信号通路关键成员，并通过荧光报告酶与基因突变法阐明该信号通路的调控机制，以期为进一步揭示胰腺癌恶性生物学行为的分子机制及早期诊断与靶向治疗位点的确定奠定良好的基础。

中文关键词： C11_胰肿瘤；肿瘤干细胞；Wnt信号通路；维吾尔族；小分子干扰RNA

英文摘要： Recent view considered that the pancreatic cancer stem cells are the core of the malignant biological behavior of pancreatic cancer. The study about the gene control of cancer stem cells also has become a new hot spot of pancreatic cancer research. Wnt signaling pathway is one of which were known to have the closest relationship with the cancer stem cells. The recently study reported that the principle members of it has abnormal expression in pancreatic cancer tissue. However, the study of dependency between Wnt signal pathway and pancreatic cancer is still in its infancy, there is only a little coverage about it. Our preliminary research show that, in pancreatic cancer tissue, there is a visible difference of the expression of Wnt signaling pathway members between Uyghur and Han patients in Xinjiang. While, does such difference also appear in pancreatic cancer stem cells? How about its regulatory mechanism? To answer the above questions, this project intends to analysis the difference of expression profile between Uyghur and Han nationality, detect the expression of mRNA and protein of Wnt signaling pathway members, and Interference with Wnt signaling pathway members' gene expression. By these methods, we will screen out the Wnt signaling pathway members which are correlation with pancreatic cancer stem cells. Then, this project also intends to illuminate the molecular biochemistry mechanism of this signal pathway by using dual-luciferase reporter assey system and gene mutation analysis. All of above research results should be conducive to revealing the molecular biochemistry mechanism of the malignant biological behavior of pancreatic cancer and finding Gene targets for early diagnosis and treatment.

英文关键词： Pancreatic cancer;Cancer stem cells;Wnt signal pathway;Uyghur;Small interfering RNA