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

Background 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. Methods 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. Results 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. Conclusions 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.

Synergistic Immunoregulation: harnessing CircRNAs and PiRNAs to Amplify PD-1/PD-L1 Inhibition Therapy

“…110 Patients with high expression level of circ_0003528 showed a worse 5-year overall survival. 110 Moreover, silence of circ_0003528 has been found to inhibit NSCLC in vivo and repress immune escape, cell viability, EMT, angiogenesis in vitro. 38 Evidence has displayed that circ_0003528 can regulate PD-L1 expression by sponging to miR-511-3p.…”

“…110 Besides, NSCLC cell lines had a higher expression of circ_0003528 than the normal lung epithelial cell lines. 110 Patients with high expression level of circ_0003528 showed a worse 5-year overall survival. 110 Moreover, silence of circ_0003528 has been found to inhibit NSCLC in vivo and repress immune escape, cell viability, EMT, angiogenesis in vitro.…”

“…Abnormal expression of Hsa_circ_0003528 in NSCLC samples was observed. 110 Briefly, as compared to matching normal lung tissues, the expression of circ_0003528 was significantly upregulated in NSCLC tissues. 110 Besides, NSCLC cell lines had a higher expression of circ_0003528 than the normal lung epithelial cell lines.…”

“…110 Briefly, as compared to matching normal lung tissues, the expression of circ_0003528 was significantly upregulated in NSCLC tissues. 110 Besides, NSCLC cell lines had a higher expression of circ_0003528 than the normal lung epithelial cell lines. 110 Patients with high expression level of circ_0003528 showed a worse 5-year overall survival.…”

“…Thus, the effects of circ_0003528 knockdown on NSCLC cell immune escape can be recovered after miR-511-3p inhibition. 110 Furthermore, miR-511-3p upregulation-mediated suppression on NSCLC cell immune escape can be partially counteracted by PD-L1 overexpression. 110 Hence, the proper way of using circ_0003528 can potentially help to augment the anti-cancer immunity.…”