MiR-217 microRNA的表达调节及其对胰腺导管腺癌生长影响的机制和其与患者预后关系的研究

项目名称： MiR-217 microRNA的表达调节及其对胰腺导管腺癌生长影响的机制和其与患者预后关系的研究

项目编号： No.U1204814

项目类型： 联合基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 赵武干

作者单位： 郑州大学

项目金额： 30万元

中文摘要： MiR-217是胰腺导管腺癌(pancreatic ductal adenocarcinoma, PDAC)中表达显著下调的microRNA。我们前期首先报导了miR-217可通过直接抑制癌基因KRAS表达而抑制肿瘤的生长。但miR-217在PDAC中表达下调的分子机制、miR-217抑制PDAC生长涉及的KRAS关键下游分子及miR-217与PDAC患者预后的关系目前还未见报导。本研拟以PDAC细胞系为材料研究miR-217表达下调的分子机制；以前期实验中构建的表达miR-217的裸鼠移植瘤组织为对象，研究miR-217在体内通过靶向KRAS抑制PDAC细胞生长的途径（生长、凋亡等）及下调KRAS抑制移植瘤生长涉及的关键下游分子；收集PDAC病人组织行miR-217杂交分析，同时对病人进行随访以分析miR-217的表达与患者预后的关系。为寻找PDAC新的治疗靶点及预后评估指标提供依据。

中文关键词： 胰腺导管腺癌；miR-217；微小RNA；预后；

英文摘要： MiR-217 is a significantly downregulated microRNA in pancreatic ductal adenocarcinoma (PDAC), and our previous work shows it can inhibit PDAC cell growth by direct targeting oncogene KRAS. Now, no researches about the molecular mechanism of miR-217 expression regulation in PDAC, the key KRAS downstream molecules involved in this tumor cell growth-inhibiting process in vivo, and the relationship between miR-217 expression and PDAC patient prognosis. In this study, we will further investigate the molecular mechanism of miR-217 expression regulation in PDAC cell, the ways (growth, apoptosis, etc) that miR-217 targeting KRAS to inhibit PDAC cell growth by in our previous constructed miR-217 harboring PDAC nude mice tissue, and the key KRAS downstream molecules involved in the tumor cell growth-inhibiting process of miR-217 in vivo. Then, we detect the expression of miR-217 in PDAC human tissue by in situ hybridization. After stratifying by different miR-217 staining intensity, follow-up data of the patients will be included to explore the prognostic significance of miR-217. From above research, we will further figure out is miR-217 a potential therapeutical target or a good prognostic parameter.

英文关键词： Pancreatic Ductal Adenocarcinoma；miR-217；microRNA；prognosis；