miR-125a-5p调控BRMS1基因表达在胃癌侵袭转移机制中的作用研究

项目名称： miR-125a-5p调控BRMS1基因表达在胃癌侵袭转移机制中的作用研究

项目编号： No.81460373

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： 揭志刚

作者单位： 南昌大学

项目金额： 47万元

中文摘要： 胃癌是我国发病率、死亡率较高的恶性肿瘤之一。腹膜转移是其预后不良的主要原因，当前关于胃癌腹膜转移的机制仍未阐明。BRMS1是一种肿瘤转移抑制基因，我们前期研究证实BRMS1 在有腹膜转移的胃癌组织中低表达，上调BRMS1 的表达能够明显降低SGC-7901细胞裸鼠胃癌模型的腹膜转移，但其调控机制尚不明确。我们通过生物信息学软件预测发现BRMS1 很可能是miR-125a-5p的靶基因，在上调胃癌细胞中miR-125a-5p的表达后，BRMS1 表达水平显著上调。因此，我们推测miR-125a-5p可以调控其靶基因BRMS1表达而影响胃癌细胞的侵袭转移。本研究拟从分子细胞及整体水平，通过观察miR-125a-5p过表达或低表达对胃癌细胞BRMS1蛋白变化及迁移侵袭能力和腹膜种植转能力的影响，探讨其具体调控机制，以求证实我们的推测。该研究的顺利完成将为胃癌腹膜转移防治提供新思路和新干预环节。

中文关键词： C07_胃肿瘤；miR-125a-5p；BRMS1；肿瘤转移

英文摘要： Gastric cancer (GC) is the main cause of cancer death in China, peritoneal metastasis indicates a poor prognosis in GC patients, but the mechanism responsible for metastatic dissemination has not been elucidated. Our previous work found that the levels of BRMS1 expression were significantly lower in GC tissue with peritoneal metastasis than in those without peritoneal metastasis. Additionally, we found that the upregulation of BRMS1 effectlively suppressed the gastric cancer cell lines invasion and migration. However, the molecular mechanisms by which BRMS1 is downregulated and promotes gastric cancer peritoneal metastasis remain to be clearly elucidated. The study on miRNAs has provides a new idea for the mechanisms of gene regulation. We found that upregulating miR-125a-5p expression increases BRMS1 protein and mRNA expression in GC cells, and miR-125a-5p likely targeting BRMS1. In this study, the effect of miR-125a-5p expression on GC cell invasion and peritoneal metastasis will be investigated in GC cell line and nude mice, also the molecular mechanism of miR-125a-5p on GC cell metastasis through targeting BRMS1 will be studied. This study will provide new strategies for prevention and treatment of GC peritoneal metastasis.

英文关键词： gastric cancer;miR-125a-5p;BRMS1;tumor metastasis