血循环microRNA-185作为一种新的食管癌诊断生物标志物及其调控食管癌细胞功能的研究

项目名称： 血循环microRNA-185作为一种新的食管癌诊断生物标志物及其调控食管癌细胞功能的研究

项目编号： No.81201349

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 崔明

作者单位： 南通大学

项目金额： 23万元

中文摘要： 肿瘤组织微小RNA（microRNA，miR）的表达不同于正常组织，其极可能释放入血，且在早期癌症患者血液中已检测到相应miR。细胞表面RAGE基因表达改变是导致肿瘤形成，组织重构的关键。本课题组首次证明食管癌组织中RAGE高表达，运用多个生物软件分析提示miR-185可能作用于RAGE。本项目拟检测不同病程和不同治疗方案的食管癌患者血浆miR-185表达，同时随访部分病例，研究血miR-185作为食管癌潜在生物标志物的诊断价值；将miR-185的Agomir激动剂，Antagomir抑制剂和对照组转染食管癌细胞和裸鼠动物模型，检测与增殖、凋亡、坏死、侵袭相关指标的含量；双荧光素酶报告基因验证miR-185是否作用于RAGE mRNA 3'非翻译区的预测靶位，并研究食管癌miR-185和RAGE表达的相关性。本研究可为探讨食管癌诊断新途径提供理论依据，并为阐明其分子发病机制提供新理念。

中文关键词： 晚期糖基化终末产物受体；microRNA-185；microRNA-182；胸部肿瘤；细胞功能

英文摘要： microRNA （miR）is differential expression between tumor and normal tissue, which can secrete into blood. Importantly, miR can be measured in the blood of early cancer patients. Deregulation of RAGE may be a critical step in tissue reorganization during formation of tumor. We first found that high expression of RAGE in esophageal cancer. By Pictar、Miranda、TargetScan, we predicted that miR-185 might target RAGE. The aim of the present study is to investigate circulating miR-185 expression in esophageal cancer of different patho-stage, types, treatments and their relationship with the clinical features. Meanwhile, we will regular follow-up some patients and study the diagnostic value of circulating miR-185 in esophageal cancer. We will transfect miR-185 Agomir, Antagomir and control into esophageal carcinoma cell and measure related index about proliferation, apoptosis, necrosis and invasion. The animal experiments will be performed. The predicted miR-185 binding site in RAGE 3'-untranslated region (UTR) will be validated by dual-luciferase reporter gene assay. We aim to investigate the correlation of miR-185 and RAGE in esophageal carcinoma. The study will provide a novel diagnostic gene and a new ideal of pathogenesis for esophageal carcinoma.

英文关键词： RAGE；microRNA-185；microRNA-182；chest tumor；cell function