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Research Paper|Volume 13, Issue 22|pp 24560—24579

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

Wen Ge1, Hao Chi1, Hua Tang2, Jianjun Xu1, Jing Wang1, Wan Cai1, Haitao Ma3
  • 1Department of Cardiothoracic Surgery, Shuguang Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, PR China
  • 2Department of Thoracic Surgery, Changzheng Hospital, Affiliated to Naval Medical University, Shanghai, PR China
  • 3Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, PR China
* Equal contribution
Received: April 6, 2021Accepted: September 3, 2021Published: November 17, 2021
https://doi.org/10.18632/aging.203576

Copyright: © 2021 Ge et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.