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. 2021 Jul;45(7):1423-1435.
doi: 10.1002/cbin.11581. Epub 2021 Apr 14.

CircKRT1 drives tumor progression and immune evasion in oral squamous cell carcinoma by sponging miR-495-3p to regulate PDL1 expression

Zhongheng Yang  1   2 , Weizhi Chen  3 , Yang Wang  1 , Mengting Qin  1 , Yanhong Ji  1
Affiliations

CircKRT1 drives tumor progression and immune evasion in oral squamous cell carcinoma by sponging miR-495-3p to regulate PDL1 expression

Zhongheng Yang et al. Cell Biol Int. 2021 Jul.

Abstract

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.

Keywords: CircKRT1; PDL1; immune evasion; miR-495-3p; oral squamous cell carcinoma.

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