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
