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

BACKGROUND: Pituitary adenoma (PA) is a common intracranial endocrine tumor, but no precise target has been found for effective prediction and treatment of PA. METHODS: Quantitative reverse transcription polymerase chain reaction (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 bioinformatic analysis including KEGG, gene ontology (GO) analysis, and microarray analysis, we evaluated the efficacy of circMFN2 as a potential biomarker for diagnosing PA, and we aimed to determine the 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 with the noninvasive 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, downregulation 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 PA.

Recurrent dynamics of rupture transitions of giant lipid vesicles at solid surfaces.

Single giant unilamellar vesicles (GUVs) rupture spontaneously from their salt-laden suspension onto solid surfaces. At hydrophobic surfaces, the GUVs rupture via a recurrent, bouncing ball rhythm. During each contact, the GUVs, rendered tense by the substrate interactions, porate, and spread a molecularly transformed motif of a monomolecular layer on the hydrophobic surface from the point of contact in a symmetric manner. The competition from pore closure, however, limits the spreading and produces a daughter vesicle, which re-engages with the substrate. At solid hydrophilic surfaces, by contrast, GUVs rupture via a distinctly different recurrent burst-heal dynamics; during burst, single pores nucleate at the contact boundary of the adhering vesicles, facilitating asymmetric spreading and producing a "heart"-shaped membrane patch. During the healing phase, the competing pore closure produces a daughter vesicle. In both cases, the pattern of burst-reseal events repeats multiple times, splashing and spreading the vesicular fragments as bilayer patches at the solid surface in a pulsatory manner. These remarkable recurrent dynamics arise, not because of the elastic properties of the solid surface, but because the competition between membrane spreading and pore healing, prompted by the surface-energy-dependent adhesion, determine the course of the topological transition.