近期研究表明环状RNA可作为“miR海绵”介入肿瘤演进，但其是否存在其他作用机制亟待研究。预实验筛选出circRNA_40753为一个致癌环状RNA，能促进胃癌细胞的生长和迁移；根据生物信息学分析及预实验结果，我们提出了一个新的功能机制：即circRNA_407533通过与APC/β-catenin蛋白复合物的直接结合，“protein sponge”APC，促进β-catenin入核进而激活Wnt信号通路。本项目拟利用多种细胞分子生物学方法通过体内体外实验阐明这一机制。最终探明（1）circRNA_40753在胃细胞中的生物学功能；（2）其是否结合APC/β-catenin蛋白复合物；（3）circRNA_40753是否激活Wnt通路。旨在揭示一个新的环状RNA“protein sponge”功能机制，为临床胃癌诊治提供新的环状RNA分子标志物和靶点。

Recently, circRNA has been shown to act as a sponge for miRNAs and play an important role in oncogenesis, however the other functional regulatory mechanism of circRNA is not clear. Based on the preliminary data, circRNA_40753 was screened as an oncogenic circRNA in gastric cancer. CircRNA_40753 promotes gastric cancer cell growth and migration. Based on the bioinformatic analysis and preliminary results, we propose a new regulatory mechanism of circRNA_40753 acting as “protein sponge”: namely circRNA_40753 contributes to the carcinogenesis and development of gastric cancer by activating Wnt signaling pathway via sponging APC from interacting with APC/β-catenin complex. .Firstly, we will evaluate the biological impact of circRNA_40753 in vitro and in vivo by transfection the overexpression plasmid or siRNA into cells followed by migration, invasion, proliferation, cell cycle, apoptosis assays, EMT and animal study. Secondly, we will confirm the interaction of circRNA_40753 with APC/β-catenin complex using FISH、RPI、RNA pull down as well as confocal immunostaining. Finally, we will explore the mechanism by which circRNA_40753 activates Wnt pathway using luciferase assay，western blot, real time PCR, CHIP, COIP and so on. The study will ultimately reveal a new regulatory mechanism of circRNA_40753 and clarify the mechanism by which circRNA_40753 promotes gastric carcinogenesis. It will ultimately provide novel circRNA molecular markers and targets for clinical diagnosis and tailored treatment of gastric cancer.