长链非编码RNA H19招募eIF4A3调控结直肠癌发生发展的分子机制研究

项目名称： 长链非编码RNA H19招募eIF4A3调控结直肠癌发生发展的分子机制研究

项目编号： No.81501998

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： 韩冬

作者单位： 哈尔滨医科大学

项目金额： 18万元

中文摘要： 长链非编码RNA(lncRNAs)在肿瘤发生发展中具有重要作用。lncRNA H19在结直肠癌中的生物学功能和分子机制鲜有报道。项目组前期研究发现H19在结直肠癌组织中显著升高，且与肿瘤分化、远端转移、分期和预后密切相关。体外实验发现H19可以促进结肠癌细胞的增殖，同时发现H19与真核翻译起始因子4A3(eIF4A3)相互作用。据此，我们提出如下假设：H19招募eIF4A3调控肿瘤关键基因的表达，从而促进结直肠癌的发生发展。本课题拟应用结直肠癌临床组织/血浆样本、结肠癌细胞体外模型和裸鼠移植瘤模型，通过RNAi干扰，基因克隆，RNA免疫共沉淀，RNA Pulldown、原位杂交等多种研究手段，并将H19表达水平和临床指标进行关联分析，从临床样本、分子、细胞以及动物整体水平深入探讨lncRNA H19在结直肠癌发生发展中的分子机制，为结直肠癌的临床治疗提供新的理论基础。

中文关键词： 结；直肠肿瘤；长链非编码RNA；H19；真核翻译起始因子4A3；肿瘤发生发展

英文摘要： Long non-coding RNAs play very important role in the development of cancer. The biological function and molecular mechanism of H19 in colorectal cancer is rarely reported. In preliminary experiment, we were excited to find the expression of H19 is upregulated in colorectal cancer tissues, which is closely related with tumor differentiation, distant metastasis, TNM stage and prognosis. We also found that H19 can promote the proliferation of colon cancer cells and there is potential interaction between H19 and eIF4A3. Therefore, we hypothesize that H19 could promote the development of colorectal cancer through the recruitment of eIF4A3, which may regulate the expression of some important oncogenes or anti-tumor genes. This study is designed to reveal the function and molecular mechanism of H19 in colorectal cancer using colorectal cancer tissue/plasma samples, cell line models in vitro, xenografts of nude mice in vivo. By the technology of RNA interference, lncRNA cloning, RNA immunoprecipitation, RNA Pulldown, in situ hybridization and the correlation analysis between H19 expression and clinical characteristic, this project is aimed at elucidating the noval mechanism of H19 in colorectal cancer and providing new therapeutic stragety for colorectal cancer.

英文关键词： colorectal cancer;long non-coding RNA;H19;eIF4A3;tumor development