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.
Highlights
Non-small cell lung cancer (NSCLC), accounting for 80% of lung cancer, is one of the malignant tumors with the highest morbidity and mortality in China [1, 2]
Inhibition of miR-124 can increase the expression of these target genes, suggesting that circHIPK3 transmits apoptosis resistance signals through the miR-124-SphK1/STAT3/CDK4 signal axis, promoting the malignant progression of lung cancer, which provides a new strategy for the treatment of NSCLC [20]
This study found that circPTK2 could regulate the transfer of NSCLC by inhibiting the expression of TIF1γ by sponge miR-429/miR-200b-3p, which enriches the mechanism of Epithelial-mesenchymal transition (EMT) induced by TGF-β
Summary
Non-small cell lung cancer (NSCLC), accounting for 80% of lung cancer, is one of the malignant tumors with the highest morbidity and mortality in China [1, 2]. It mainly comprises adenocarcinoma (65%) and squamous cell carcinoma (30%) histologies. Immunotherapy has greatly improved the prognosis of adenocarcinomas and squamous cell carcinomas, whereas the treatment of targetable driver mutations, has so far only benefited adenocarcinomas [1, 2]. The clinical signs are not specific, so the vast majority of patients have been confirmed to be late stage at the time of diagnosis and are not suitable for surgical treatment. We need to further explore more markers for clinical diagnosis and therapy of NSCLC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
