Circ_0008287 promotes immune escape of gastric cancer cells through impairing microRNA-548c-3p-dependent inhibition of CLIC1

下调和上调 癌细胞 癌症 免疫系统 癌变 癌症研究 基因沉默 流式细胞术 CD8型 小RNA 细胞凋亡 转移 生物 化学 分子生物学 免疫学 基因 生物化学 遗传学
作者
Bopei Li,Liang Liang,Yeyang Chen,Jinlu Liu,Zhen Wang,Yuantian Mao,Kun Zhao,Junqiang Chen
出处
期刊:International Immunopharmacology [Elsevier]
卷期号:111: 108918-108918 被引量:10
标识
DOI:10.1016/j.intimp.2022.108918
摘要

Analyses in silico suggested the upregulation of a circular RNA (circRNA), circ_0008287, in gastric cancer and possible interactions among microRNA (miR)-548c-3p, circ_0008287, and intracellular chloride channel protein 1 (CLIC1). This study aims to testify whether circ_0008287 can affect the immune escape of gastric cancer cells by regulating miR-548c-3p and CLIC1.RT-qPCR was performed to determine the expression pattern of circ_0008287 in gastric cancer cells. Gain- and loss-of function assays were then performed to assess the effects of circ_0008287 on malignant phenotypes of cancer cells. Interactions among circ_0008287, miR-548c-3p and CLIC1 were verified by dual luciferase reporter gene, RIP and FISH assays. Effects of CLIC1 on IFN-γ secretion and apoptosis in CD8 + T cells were evaluated by flow cytometry following co-culture of CD8 + T cells with cancer cells overexpressing/silencing CLIC1. A gastric cancer mouse model was further developed for in vivo investigation on effects of circ_0008287 on tumorigenesis and tumor metastasis.circ_0008287, an upregulated circRNA in gastric cancer cells, augmented the viability as well as invasive and migratory potentials of gastric cancer cells. By competitively binding to miR-548c-3, circ_0008287 increased the expression of CLIC1, which impaired the function of CD8 + T cells and promoted their apoptosis. After downregulation of circ_0008287, in vivo tumorigenesis and metastasis were suppressed.Hence, this study suggests the promotive role of circ_0008287 in gastric cancer progression and immune escape and further elucidates the underlying circ_0008287/miR-548c-3p/CLIC1 regulatory axis.
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