CircRNA4779/miR-126/miR-762轴调控胃癌干细胞免疫微环境促进胃癌转移的作用和机制

胃癌的转移严重影响患者的预后。环状RNA（circRNA）与胃癌转移的关系仍知之甚少。前期高通量实验结果提示circRNA4779在miR-126敲降表达的胃癌细胞中显著升高，与下调的miR-762一并处于circRNA-miRNA网络调控的核心位置。干扰素调控因子7（IRF7）可调控肿瘤相关巨噬细胞（TAM）的极化。预实验证实miR-762可靶向负调控IRF7。我们合理推测胃癌中存在一条circRNA4779/miR-126/miR-762调控轴，即：CircRNA4779可能吸附下调miR-126的表达而促进miR-762的表达，后者通过靶向负调控IFR7的表达促进TAM的M2极化增加，最终促进胃癌的转移。本项目拟从细胞、组织及动物整体水平探讨circRNA4779在胃癌免疫微环境及转移中的重要作用，明确circRNA4779介导miR-126/miR-762通路对胃癌转移的调控机制。

Gastric cancer metastasis seriously affects the quality of life and prognosis of patients.Circular RNA ( circRNA ) is a new type of RNA that plays critical roles in multiple biological processes discovered in recent years. However, there is still lack of investigation about the role of circRNA in gastric cancer metastasis. Our results showed that circRNA4779 exhibited significant upregulation accompanied with the downregulation of miR-762 in gastric cancer cell line inhibited the expression of miR-126 by lenti-anti-miR-126 transfection . The specific mechanism of its role of circRNA4779 in gastric cancer metastasis still needs further exploration. Previous studies revealed that interferon regulating factor 7 (IRF7) played important role in the regulation of tumor associated macrophage M1/M2 polarization. Thus, we hypothesized that circRNA4779 may regulate gastric cancer stem cell immune microenvironment through miR-126/miR-762/IRF7 pathway to affect gastric cancer metastasis. To verify this hypothesis, we used gastric cancer cell lines, nude mice, and clinical gastric cancer tissue to investigate the function of circRNA4779 in gastric cancer metastasis by using real-time PCR, ELISA, and flow cytometry. This study explored the mechanism of gastric cancer metastasis from the aspect of circRNA4779, which may supply new thought for the treatment and prevention of gastric cancer.