Manian Mostafa, Sohrabi Ehsan, Eskandari Nahid, Assarehzadegan Mohammad-Ali, Ferns Gordon A, Nourbakhsh Mitra, Jazayeri Mir Hadi, Nedaeinia Reza
Department of Immunology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Avicenna J Med Biotechnol. 2021 Jul-Sep;13(3):149-165. doi: 10.18502/ajmb.v13i3.6364.
Overexpression of miR-21 is a characteristic feature of patients with Multiple Sclerosis (MS) and is involved in gene regulation and the expression enhancement of pro-inflammatory factors including IFNγ and TNF-α following stimulation of T-cells the T Cell Receptor (TCR). In this study, a novel integrated bioinformatics analysis was used to obtain a better understanding of the involvement of miR-21 in the development of MS, its protein biomarker signatures, RNA levels, and drug interactions through existing microarray and RNA-seq datasets of MS.
In order to obtain data on the Differentially Expressed Genes (DEGs) in patients with MS and normal controls, the GEO2R web tool was used to analyze the Gene Expression Omnibus (GEO) datasets, and then Protein-Protein Interaction (PPI) networks of co-expressed DEGs were designed using STRING. A molecular network of miRNA-genes and drugs based on differentially expressed genes was created for T-cells of MS patients to identify the targets of miR-21, that may act as important regulators and potential biomarkers for early diagnosis, prognosis and, potential therapeutic targets for MS.
It found that seven genes (NRIP1, ARNT, KDM7A, S100A10, AK2, TGFβR2, and IL-6R) are regulated by drugs used in MS and miR-21. Finally, three overlapping genes (S100A10, NRIP1, KDM7A) were identified between miRNA-gene-drug network and nineteen genes as hub genes which can reflect the pathophysiology of MS.
Our findings suggest that miR-21 and MS-related drugs can act synergistically to regulate several genes in the existing datasets, and miR-21 inhibitors have the potential to be used in MS treatment.
miR-21的过表达是多发性硬化症（MS）患者的一个特征，并且在基因调控以及T细胞受体（TCR）刺激后促炎因子（包括IFNγ和TNF-α）的表达增强中发挥作用。在本研究中，我们使用了一种新型的综合生物信息学分析方法，通过现有的MS微阵列和RNA测序数据集，来更好地了解miR-21在MS发展中的作用、其蛋白质生物标志物特征、RNA水平以及药物相互作用。
为了获取MS患者和正常对照中差异表达基因（DEG）的数据，使用GEO2R网络工具分析基因表达综合数据库（GEO）数据集，然后使用STRING设计共表达DEG的蛋白质-蛋白质相互作用（PPI）网络。基于差异表达基因创建了MS患者T细胞的miRNA-基因和药物分子网络，以识别miR-21的靶标，这些靶标可能作为MS早期诊断、预后的重要调节因子和潜在生物标志物，以及潜在的治疗靶点。
发现七个基因（NRIP1、ARNT、KDM7A、S100A10、AK2、TGFβR2和IL-6R）受MS中使用的药物和miR-21调控。最后，在miRNA-基因-药物网络之间鉴定出三个重叠基因（S100A10、NRIP1、KDM7A），以及19个作为枢纽基因的基因，它们可以反映MS的病理生理学。
我们的研究结果表明，miR-21和MS相关药物可以协同作用来调节现有数据集中的多个基因，并且miR-21抑制剂有潜力用于MS治疗。
