Circular RNA CELF1 drives immunosuppression and anti-PD1 therapy resistance in non-small cell lung cancer via the miR-491-5p/EGFR axis

Aim: To explore the immunoregulatory effects of circ_CELF1 in non-small cell lung cancer (NSCLC). Methods: The mRNA level of circ_CELF1 in primary tissue samples was analyzed by qRT-PCR. The assays of CCK-8, colony formation, wound healing as well as Transwell were employed for measurement of cancer cell malignant transformation. The murine subcutaneous tumor model was used to assess the tumorigenesis of NSCLC in vivo. The assays of circRNA precipitation, RNA immunoprecipitation, and luciferase reporter were performed to study the relationship between circ_CELF1, miR-491-5p, and EGFR. Results: circ_CELF1 is upregulated in primary cancer tissues from patients with NSCLC, and a high level of circ_CELF1, is associated with malignant characteristics and poor outcomes of patients with NSCLC. Enforced expression of circ_CELF1 exacerbated the malignant transformation of NSCLC cells. Mechanistically, through directly interacting with miR-491-5p, circ_CELF1 acted as a miRNA sponge that increased the expression of the miR-491-5p target gene EGFR, eventually promoting the progression of NSCLC and increasing cancer resistance to immunotherapy. Conclusion: Our data demonstrate that upregulation of circ_CELF1 elicits both oncogenic and immunoregulatory effects on the development of NSCLC. We believe that circ_CELF1 can act as a potential therapeutic target for the treatment of NSCLC.