CircFOXK2 enhances tumorigenesis and immune evasion in non-small cell lung cancer by miR-485-5p/PD-L1 axis.

Abstract

Circular RNAs (circRNAs) serve a key role in lots of cancers. The outcomes of upregulated circular RNA forkhead box K2 (circFOXK2) on non-small cell lung cancer (NSCLC) persisted uncertainly. In this study, the role of circFOXK2 in NSCLC was inspected. The abundances of circFOXK2, microRNA-485-5p (miR-485-5p) and programmed cell death ligand-1 (PD-L1) were confirmed by quantitative real-time PCR and western blot. Cell counting kit-8 (CCK-8) assay and clonogenic assay were accomplished to conclude the proliferation of NSCLC cells. Wound healing and transwell assays were implemented to evaluate cell migration and invasion. Lactate dehydrogenase (LDH) cytotoxicity assay was enforced to quantify the cytotoxicity of CD8+ T cells. Flow cytometry assay was employed to detect apoptosis. Besides, the mice experiments were utilized for in vivo tumorigenesis analysis. Dual-luciferase reporter assay was carried out to reveal the associations between miR-485-5p and circFOXK2 or PD-L1. CircFOXK2 and PD-L1 levels were augmented in NSCLC. CircFOXK2 targeted miR-485-5p, which could bind to PD-L1. CircFOXK2 served a key role in NSCLC tumorigenesis and cytotoxicity of CD8+ T cells. MiR-485-5p inhibition or PD-L1 overexpression abolished the inhibitory effects of circFOXK2 lack on NSCLC tumorigenesis and cytotoxicity of CD8+ T cells. CircFOXK2 sponged miR-485-5p to stimulate PD-L1 and expedited NSCLC development.