Exosomal CircMFN2 Enhances the Progression of Pituitary Adenoma Via The MiR-146a-3p/TRAF6/NF-κB Pathway

Abstract

Background: Pituitary adenoma (PA) is a common intracranial endocrine cancer, but no precise target has been found for the effective prediction and treatment of PA. Methods: qRT‒PCR analysis showed that circMFN2 could affect the expression of miR-146a-3p in PA samples. Moreover, we used Western blotting to evaluate the expression levels of TRAF6 and NF-κB markers. The EdU assay, scratch wound-healing assay, and matrigel invasion assay were performed to assess the potential function of this pathway in PA cells. Based on the bioinformatics analysis including KEGG, GO analysis and microarray analysis, we evaluated the efficacy of circMFN2 as a potential biomarker for diagnosing PA, and we aimed to determine it mechanism of action in PA cells. Results: Our findings indicate that there is a significant increase in the expression of circMFN2 in tissues, serum, and exosomes in the invasive group compared to the non-invasive and normal groups. Furthermore, this difference was statistically significant both preoperatively and postoperatively. To clarify its function, we downregulated this gene, and the experimental results suggested that the motility and proliferative capacity were reduced in vitro. In addition, rescue assays showed that miR-146a-3p could successfully reverse the inhibitory effect of circMFN2 knockdown on motility and proliferation in PA cells. Moreover, down-regulation of circMFN2 and miR-146a-3p significantly changed the expression of TRAF6 and NF-κB. Conclusion: This study identified that circMFN2 regulates miR-146a-3p to promote adenoma development partially via the TRAF6/NF-κB pathway and may be a potential therapeutic target for pituitary adenoma.