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CC BY-NC-ND 4.0 · J Neurol Surg A Cent Eur Neurosurg
DOI: 10.1055/a-2201-8370
Original Article

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

Haitong Wan
1   Department of Neurosurgery, First Affiliated Hospital of Medical College, Shihezi University, Shihezi, China
,
Xiang Gao
1   Department of Neurosurgery, First Affiliated Hospital of Medical College, Shihezi University, Shihezi, China
,
Zexu Yang
2   Department of Neurosurgery, First Affiliated Hospital of Medical College, Shihezi University, Shihezi, China
,
Leiguo Wei
2   Department of Neurosurgery, First Affiliated Hospital of Medical College, Shihezi University, Shihezi, China
,
Yufei Qu
2   Department of Neurosurgery, First Affiliated Hospital of Medical College, Shihezi University, Shihezi, China
,
Qi Liu 
2   Department of Neurosurgery, First Affiliated Hospital of Medical College, Shihezi University, Shihezi, China
› Author Affiliations Funding This study was supported by the XPCC Science and Technology Plan of Science and Technology Innovation Talent Program (2022CB002–09) to Qi Liu.
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Abstract

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.

Keywords

pituitary adenoma - circMFN2 - miRNA - exosome - biomarker

Availability of Data and Materials

We guarantee the authenticity and validity of all data and results. Open up some of the raw data uploads as supplementary files.


Ethics Approval

All the patients' blood and tissue were collected after obtaining written signed informed consent and validated by the Ethics Committee of The First Affiliated Hospital of Medical College of Shihezi (KJ2021–076–02).


Informed Consent

Informed consent was obtained from all individuals included in this study.


Author Contributions

Q.L. contributed to project management and manuscript editing. H.W. completed the manuscript writing and data analysis and performed an experiment. X.G. was involved in clinical sample collection. Z.Y. assisted in the investigation. L.W. and Y.Q. designed the experiment. All the authors reviewed the article.


Supplementary Material



Publication History

Received: 06 August 2023

Accepted: 24 October 2023

Accepted Manuscript online:
31 October 2023

Article published online:
16 February 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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