Karimi Nafiseh, Motovali Bashi Majid, Ghaderi-Zefrehei Mostafa, Lesch Bluma J
Department of Cell and Molecular Biology, Faculty of Biological Science, University of Isfahan, Isfahan, Iran.
Department of Animal Sciences, Faculty of Agriculture, Yasouj University, Yasouj, Iran.
Iran J Med Sci. 2025 Jul 1;50(7):472-480. doi: 10.30476/ijms.2024.103243.3647. eCollection 2025 Jul.
An incapacitating chronic inflammatory neurodegenerative illness, known as multiple sclerosis (MS), is characterized by lymphocyte infiltration into the central nervous system. We aimed to identify specific miRNAs whose altered expression correlates with MS diagnosis and therapy selection, which could be biomarkers for these aspects of the disease.
The GSE21079 dataset was obtained for this study using Geoquery version 2.50.5 from the Gene Expression Omnibus database. The miRNAs exhibiting the highest variance were selected, and a miRNA-miRNA interaction network was constructed through a Bayesian network utilizing the bnlearn R package (version 4.7.1). The adjacency matrix generated from the learned network was subsequently analyzed in the Cytoscape environment. For the workbench lab, whole blood samples were collected from the MS Research Center and Al-Zahra Hospital in Isfahan, Iran, between June 2019 and October 2019. RNA extraction was conducted in the laboratory at Isfahan University. Real-time PCR (RT-PCR) was employed to validate the expression changes of the candidate mirRNAs (, ). The results were analyzed using REST 2009 software.
The Notch1 signaling pathway was targeted by and in MS patients, which led to downregulation of critical genes, such as and , , and . Furthermore, the results from RT-PCR among 50 whole blood samples, comprising 30 cases of MS and 20 control cases, indicated that the expression levels of miRNA in patients with MS exhibited a statistically significant difference compared to those in healthy individuals, with values of 0.324 for and 0.075 for . These values correspond to a downregulation of 3.1-fold and 13.3-fold, respectively.
The findings indicate that MS patients have lower expression levels of and .
多发性硬化症（MS）是一种使人衰弱的慢性炎症性神经退行性疾病，其特征是淋巴细胞浸润中枢神经系统。我们旨在鉴定特定的微小RNA（miRNA），其表达改变与MS诊断和治疗选择相关，这可能是该疾病这些方面的生物标志物。
本研究使用来自基因表达综合数据库的Geoquery版本2.50.5获取GSE21079数据集。选择表现出最高方差的miRNA，并使用bnlearn R包（版本4.7.1）通过贝叶斯网络构建miRNA-miRNA相互作用网络。随后在Cytoscape环境中分析从学习到的网络生成的邻接矩阵。对于工作台实验室，于2019年6月至2019年10月期间从伊朗伊斯法罕的MS研究中心和阿尔-扎赫拉医院采集全血样本。在伊斯法罕大学实验室进行RNA提取。采用实时聚合酶链反应（RT-PCR）验证候选mirRNA（，）的表达变化。使用REST 2009软件分析结果。
在MS患者中，Notch1信号通路被和靶向，这导致关键基因如、、和的下调。此外，在50个全血样本（包括30例MS病例和20例对照病例）中进行的RT-PCR结果表明，MS患者中miRNA的表达水平与健康个体相比具有统计学显著差异，的值为0.324，的值为0.075。这些值分别对应3.1倍和13.3倍的下调。
研究结果表明MS患者的和表达水平较低。
