生物
癌症研究
基因敲除
流式细胞术
免疫系统
CD8型
肿瘤进展
细胞凋亡
下调和上调
细胞生长
细胞
小RNA
分子生物学
癌症
免疫学
基因
生物化学
遗传学
作者
Zhongheng Yang,Weizhi Chen,Yang Wang,Momei Qin,Yanhong Ji
摘要
Regulatory functions of circRNAs by targeting the micro RNA (miRNA)/mRNA axis have been increasingly found in oral squamous cell carcinoma (OSCC). CircRNA keratin 1 (CircKRT1) and miR-495-3p were dysregulated in OSCC. Programmed death ligand 1 (PDL1) was an important immunotherapeutic molecule in OSCC. Our objective was to explore whether circKRT1 could regulate cancer progression and immune evasion in OSCC by affecting the miR-495-3p/PDL1 axis. RNA expression was examined by quantitative real-time polymerase chain reaction. All protein levels were detected by western blot. OSCC cell growth was assessed by CCK-8 and colony formation assays. Cell migratory and invasive abilities were evaluated by transwell assay. CD8+ T-cell cytotoxicity was determined via lactate dehydrogenase assay. CD8+ T-cell percentage and apoptosis were analyzed by flow cytometry. Target screening was performed by Veen Diagram and RNA pull-down assay. Target binding was verified using dual-luciferase reporter and RNA immunoprecipitation assays. A xenograft in mice was conducted for in vivo experiment. CircKRT1 and PDL1 were highly expressed in OSCC tissues and cells. CircKRT1 knockdown repressed OSCC cell growth, migration, invasion, epithelial-mesenchymal transition, and CD8+ T-cell apoptosis, but enhanced CD8+ T cytotoxicity and percentage. The inhibitory effects of circKRT1 downregulation on OSCC progression and immune evasion were related to PDL1 expression inhibition. CircKRT1 sponged miR-495-3p and miR-495-3p targeted PDL1. OSCC progression and immune evasion were regulated by circKRT1 via the miR-495-3p/PDL1 axis. CircKRT1 also facilitated OSCC progression in vivo by regulating miR-495-3p and PDL1. This study clarified that circKRT1 worked as a miR-495-3p sponge to regulate PDL1, consequently affecting cancer progression and immune evasion in OSCC.
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