Hsa_circ_0003528 promotes cell malignant transformation and immune escape via increasing oncogene PDL1 through sponging miR‐511‐3p in non‐small cell lung cancer

Abstract

Accumulating evidence suggests that circular RNAs (circRNAs) play important regulatory roles in non-small cell lung cancer (NSCLC). At present, we aimed to explore the regulatory role of has_circ_0003528 (circ_0003528) in NSCLC. Alterations of circ_0003528 expression in NSCLC samples and cell lines were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Impacts of circ_0003528 on NSCLC cell malignant transformation were analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell invasion, and tube formation assays. Epithelial-mesenchymal transition (EMT)-related markers were detected with western blotting. Pro-inflammatory cytokines were detected by Enzyme-linked immunosorbent assay (ELISA). The regulation mechanism of circ_0003528 was verified by dual-luciferase reporter and RNA pull-down assays. The tumorigenesis role of circ_0003528 was verified by animal experiments. Higher levels of circ_0003528 were obtained in NSCLC samples and cell lines, and patients with high circ_0003528 expression had a worse prognosis. Silence of circ_0003528 decreased xenograft growth in mouse models and induced cell apoptosis and repressed cell viability, proliferation, invasion, EMT, angiogenesis, and immune escape in NSCLC cells in vitro. Mechanistically, circ_0003528 controlled programmed cell death ligand 1 (PDL1) expression through interaction with miR-511-3p. The inhibiting impacts of circ_0003528 knockdown on NSCLC cell malignant transformation and immune escape were weakened after miR-511-3p silencing. Moreover, PDL1 overexpression partially counteracted miR-511-3p upregulation-mediated suppression on NSCLC cell malignant transformation and immune escape. Circ_0003528 facilitated NSCLC cell malignant transformation and immune escape through regulation of the miR-511-3p/PDL1 axis, highlighting the oncogenic role of circ_0003528 in NSCLC.