RGS2-Related Non-coding Interaction Network Modulates the NF-Kappa B Signaling Pathway in MS Patients: A Systems Biology Investigation

IF 2.7 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Parisa Forouzanfar, Mohammad Hashemian, Mojdeh Mahmoudian, Melika Khorsandi, Mohammad Rezaei, Mansoureh Azadeh
{"title":"RGS2-Related Non-coding Interaction Network Modulates the NF-Kappa B Signaling Pathway in MS Patients: A Systems Biology Investigation","authors":"Parisa Forouzanfar,&nbsp;Mohammad Hashemian,&nbsp;Mojdeh Mahmoudian,&nbsp;Melika Khorsandi,&nbsp;Mohammad Rezaei,&nbsp;Mansoureh Azadeh","doi":"10.1007/s12031-025-02413-9","DOIUrl":null,"url":null,"abstract":"<div><p>Multiple sclerosis (MS) is the most common chronic inflammatory disease affecting the brain and spinal cord, with approximately 2.8 million cases globally. This study analyzed high-throughput MS datasets to identify dysregulated RNAs and visualized novel RNA regulatory networks to uncover non-coding interactions in MS-related signaling pathways. High-throughput gene expression datasets were analyzed in R Studio to identify dysregulated mRNAs in MS patients. miRNA, lncRNA, and protein interactions were explored using miRWalk and lncRRIsearch. Pathway enrichment analysis was performed via Enrichr and KEGG, and qRT-PCR validated the gene expression results. RGS2 was found to be significantly upregulated in both microarray (logFC: 1.7667, adj.P. Value: 0.0079) and qRT-PCR analyses (logFC: 4.547, <i>p</i>-value &lt; 0.0001). Similarly, the lncRNAs NCK1-DT (logFC: 2.155, <i>p</i>-value: 0.0132) and ASH1L-AS1 (logFC: 3.345, <i>p</i>-value &lt; 0.0001) exhibited elevated expression in MS samples, suggesting a regulatory impact on RGS2 expression levels. The marked changes in the expression of RGS2, NCK1-DT, and ASH1L-AS1 in MS patients compared to normal samples position them as promising diagnostic biomarkers. Additionally, RGS2 and its associated proteins have been implicated in modulating the NF-Kappa B signaling pathway. MiR-4638-3p was identified to directly downregulate RGS2 expression, while miR-4525 influences the expression of RGS2 and ASH1L-AS1 within a competing endogenous RNA (ceRNA) network. NCK1-DT and ASH1L-AS1 are the two novel diagnostic biomarkers of MS. Mentioned lncRNAs might affect the normal regulatory mechanisms of “NF-Kappa B signaling pathway” through direct and indirect interaction with mRNA RGS2.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 4","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s12031-025-02413-9","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Multiple sclerosis (MS) is the most common chronic inflammatory disease affecting the brain and spinal cord, with approximately 2.8 million cases globally. This study analyzed high-throughput MS datasets to identify dysregulated RNAs and visualized novel RNA regulatory networks to uncover non-coding interactions in MS-related signaling pathways. High-throughput gene expression datasets were analyzed in R Studio to identify dysregulated mRNAs in MS patients. miRNA, lncRNA, and protein interactions were explored using miRWalk and lncRRIsearch. Pathway enrichment analysis was performed via Enrichr and KEGG, and qRT-PCR validated the gene expression results. RGS2 was found to be significantly upregulated in both microarray (logFC: 1.7667, adj.P. Value: 0.0079) and qRT-PCR analyses (logFC: 4.547, p-value < 0.0001). Similarly, the lncRNAs NCK1-DT (logFC: 2.155, p-value: 0.0132) and ASH1L-AS1 (logFC: 3.345, p-value < 0.0001) exhibited elevated expression in MS samples, suggesting a regulatory impact on RGS2 expression levels. The marked changes in the expression of RGS2, NCK1-DT, and ASH1L-AS1 in MS patients compared to normal samples position them as promising diagnostic biomarkers. Additionally, RGS2 and its associated proteins have been implicated in modulating the NF-Kappa B signaling pathway. MiR-4638-3p was identified to directly downregulate RGS2 expression, while miR-4525 influences the expression of RGS2 and ASH1L-AS1 within a competing endogenous RNA (ceRNA) network. NCK1-DT and ASH1L-AS1 are the two novel diagnostic biomarkers of MS. Mentioned lncRNAs might affect the normal regulatory mechanisms of “NF-Kappa B signaling pathway” through direct and indirect interaction with mRNA RGS2.

rgs2相关的非编码相互作用网络调节MS患者NF-Kappa B信号通路:系统生物学研究
多发性硬化症(MS)是影响大脑和脊髓的最常见的慢性炎症性疾病,全球约有280万例。本研究分析了高通量MS数据集,以鉴定失调的RNA,并可视化了新的RNA调控网络,以揭示MS相关信号通路中的非编码相互作用。在R Studio中分析高通量基因表达数据集,以识别MS患者中失调的mrna。使用miRWalk和lncRRIsearch研究miRNA、lncRNA和蛋白质相互作用。通过enrichment和KEGG进行途径富集分析,qRT-PCR验证基因表达结果。RGS2在两个基因芯片中均显著上调(logFC: 1.7667, adj.P.)。值:0.0079)和qRT-PCR分析(logFC: 4.547, p值<; 0.0001)。同样,lncRNAs NCK1-DT (logFC: 2.155, p值:0.0132)和ASH1L-AS1 (logFC: 3.345, p值<; 0.0001)在MS样品中表达升高,表明对RGS2表达水平有调节作用。与正常样本相比,MS患者中RGS2、NCK1-DT和ASH1L-AS1表达的显著变化使它们成为有希望的诊断生物标志物。此外,RGS2及其相关蛋白参与调节NF-Kappa B信号通路。MiR-4638-3p被鉴定为直接下调RGS2表达,而miR-4525在竞争性内源性RNA (ceRNA)网络中影响RGS2和ASH1L-AS1的表达。NCK1-DT和ASH1L-AS1是ms的两种新的诊断性生物标志物,上述lncrna可能通过与mRNA RGS2的直接或间接相互作用影响“NF-Kappa B信号通路”的正常调控机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Journal of Molecular Neuroscience
Journal of Molecular Neuroscience 医学-神经科学
CiteScore
6.60
自引率
3.20%
发文量
142
审稿时长
1 months
期刊介绍: The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信