miR-490-3p调控剂(ANOS)抗幽门螺旋杆菌诱发胃癌的作用研究

项目名称： miR-490-3p调控剂(ANOS)抗幽门螺旋杆菌诱发胃癌的作用研究

项目编号： No.81503093

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： 肖占刚

作者单位： 西南医科大学

项目金额： 17.9万元

中文摘要： microRNA通过调节众多基因表达来行使致癌或抑癌功能，使得microRNA在肿瘤治疗中常成为有效靶标。调节microRNA表达的小分子化合物被视为潜在的抗癌药物。申请人前期研究详细阐述了miR-490-3p作为抑癌基因在幽门螺旋杆菌(Hp)诱发胃癌中的作用机制。过表达miR-490-3p抑制胃癌效应显著。因此，激活miR-490-3p表达的调控剂可成为抗Hp诱发胃癌的潜在药物。我们通过生物信息学方法比对miR-490-3p模拟物处理胃癌细胞和1309种小分子化合物分别处理细胞得到的人类全基因芯片数据，发现了一个呈剂量依赖激活miR-490-3p表达的小分子化合物。该化合物被命名为ANOS。初步的体内、体外实验显示ANOS具有明显的抗胃癌活性。本研究旨在探索ANOS是否具有预防、延迟和抑制Hp诱发胃癌的效果及探讨ANOS调控miR-490-3p表达的作用机制。

中文关键词： 胃肿瘤；幽门螺旋杆菌；微小RNA；小分子化合物；抗癌药物

英文摘要： MicroRNAs function as oncogenes or tumor suppressors by regulating gene expression and represent promising therapeutic targets for cancer. Small molecules modulating microRNAs expressions would thus constitute potential anticancer agents. In our previous study, we found that microRNA-490-3p (miR-490-3p) functioned as a tumor suppressor and was downregulated in Helicobacter pylori （Hp） induced gastric cancer. The mechanism of the role of miR-490-3p in Hp induced gastric cancer was also well elucidated. Since overexpression of miR-490-3p exhibited high anti-gastric cancer efficency, small molecule activating miR-490-3p expression would thus constitute potential anti-Hp induced gastric cancer agent. In our previous studies, by comparing and analyzing the microarray data from miR-490-3p treated gastric cancer cells and 1309 compounds treated cells, we found that a small molecule termed ANOS activiated miR-490-3p expression in a dose dependant manner. ANOS exhibited anti-gastric cancer activity both in in vitro and in vivo. In this project, we will focus on the function of ANOS on prevention,delay and inhibition of Hp induced gastric cancer and try to illustrate the detailed mechanism on how ANOS activates the expression of miR-490-3p.

英文关键词： gastric cancer;Helicobacter pylori;microRNA;small molecue compound;anti-cancer agent