研究动态
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外泌体 CircMFN2 通过 MiR-146a-3p/TRAF6/NF-κB 途径促进垂体腺瘤的进展。

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

发表日期:2023 Oct 31
作者: 海彤 Wan, Xiang Gao, Zexu Yang, Leiguo Wei, Yufei Qu, Qi Liu
来源: Cellular & Molecular Immunology

摘要:

垂体腺瘤(PA)是一种常见的颅内内分泌癌,但目前尚未找到有效预测和治疗PA的精确靶点。qRT-PCR分析显示,circMFN2可以影响PA样本中miR-146a-3p的表达。此外,我们使用蛋白质印迹法来评估TRAF6和NF-κB标记物的表达水平。进行 EdU 测定、划痕伤口愈合测定和基质胶侵袭测定来评估该通路在 PA 细胞中的潜在功能。基于KEGG、GO分析和微阵列分析等生物信息学分析,我们评估了circMFN2作为诊断PA的潜在生物标志物的功效,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,circMFN2显着增加与非侵袭组和正常组相比,侵袭组的组织、血清和外泌体中 circMFN2 的表达情况。此外,这种差异在术前和术后均具有统计学意义。为了阐明其功能,我们下调了该基因,实验结果表明体外运动性和增殖能力降低。此外,救援实验表明,miR-146a-3p 可以成功逆转 circMFN2 敲低对 PA 细胞运动和增殖的抑制作用。此外,circMFN2和miR-146a-3p的下调显着改变了TRAF6和NF-κB的表达。本研究发现,circMFN2部分通过TRAF6/NF-κB途径调节miR-146a-3p促进腺瘤的发展,并且可能是垂体腺瘤的潜在治疗靶点。作者。这是蒂姆根据知识共享署名-非衍生-非商业许可条款发表的开放获取文章,只要对原始作品给予适当的署名,就允许复制和复制。内容不得用于商业目的,也不得改编、重新混合、转换或构建。 (https://creativecommons.org/licenses/by-nc-nd/4.0/)。
Pituitary adenoma (PA) is a common intracranial endocrine cancer, but no precise target has been found for the effective prediction and treatment of PA.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.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.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.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/).