Wan Haitong, Gao Xiang, Yang Zexu, Wei Leiguo, Qu Yufei, Liu Qi
Department of Neurosurgery, First Affiliated Hospital of Medical College, Shihezi University, Shihezi, China.
J Neurol Surg A Cent Eur Neurosurg. 2025 Mar;86(2):135-147. doi: 10.1055/a-2201-8370. Epub 2023 Oct 31.
Pituitary adenoma (PA) is a common intracranial endocrine tumor, but no precise target has been found for effective prediction and treatment of PA.
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.
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.
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.
垂体腺瘤（PA）是一种常见的颅内内分泌肿瘤，但尚未找到用于有效预测和治疗PA的精确靶点。
定量逆转录聚合酶链反应（qRT‒PCR）分析表明，环状线粒体融合蛋白2（circMFN2）可影响PA样本中miR-146a-3p的表达。此外，我们使用蛋白质免疫印迹法评估肿瘤坏死因子受体相关因子6（TRAF6）和核因子κB（NF-κB）标志物的表达水平。进行5-乙炔基-2'-脱氧尿苷（EdU）检测、划痕愈合检测和基质胶侵袭检测，以评估该信号通路在PA细胞中的潜在功能。基于包括京都基因与基因组百科全书（KEGG）、基因本体（GO）分析和微阵列分析在内的生物信息学分析，我们评估了circMFN2作为诊断PA潜在生物标志物的有效性，并旨在确定其在PA细胞中的作用机制。
我们的研究结果表明，与非侵袭组和正常组相比，侵袭组组织、血清和外泌体中circMFN2的表达显著增加。此外，术前和术后这种差异均具有统计学意义。为阐明其功能，我们下调了该基因，实验结果表明体外迁移和增殖能力降低。此外，拯救实验表明，miR-146a-3p可成功逆转circMFN2敲低对PA细胞迁移和增殖的抑制作用。此外，circMFN2和miR-146a-3p的下调显著改变了TRAF6和NF-κB的表达。
本研究发现circMFN2通过TRAF6/NF-κB信号通路部分调节miR-146a-3p以促进腺瘤发展，可能是PA的潜在治疗靶点。
