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LncRNA‐miRNA network analysis across the Th17 cell line reveals biomarker potency of lncRNA NEAT1 and KCNQ1OT1 in multiple sclerosis
Authors:Elham Karimi  Hanieh Azari  Ahmad Tahmasebi  Amin Reza Nikpoor  Ahmad Agha Negahi  Nima Sanadgol  Mohammad Shekari  Pegah Mousavi
Institution:1. Department of Medical Genetics, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas Iran ; 2. Institute of Biotechnology, Shiraz University, Shiraz Iran ; 3. Sciences Research Center for Molecular Medicine, Hormozgan University of Medical, Hormozgan Iran ; 4. Department of Internal Medicine, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas Iran ; 5. Institute of Neuroanatomy, RWTH University Hospital Aachen, Aachen Germany
Abstract:Differentiation of CD4+ T cells into Th17 cells is an important factor in the onset and progression of multiple sclerosis (MS) and Th17/Treg imbalance. Little is known about the role of lncRNAs in the differentiation of CD4+ cells from Th17 cells. This study aimed to analyse the lncRNA‐miRNAs network involved in MS disease and its role in the differentiation of Th17 cells. The lncRNAs in Th17 differentiation were obtained from GSE66261 using the GEO datasets. Differential expression of lncRNAs in Th17 primary cells compared to Th17 effector cells was investigated by RNA‐seq analysis. Next, the most highlighted lncRNAs in autoimmune diseases were downloaded from the lncRNAs disease database, and the most critical miRNA was extracted by literature search. Then, the lncRNA‐miRNA interaction was achieved by the Starbase database, and the ceRNA network was designed by Cytoscape. Finally, using the CytoHubba application, two hub lncRNAs with the most interactions with miRNAs were identified by the MCODE plug‐in. The expression level of genes was measured by qPCR, and the plasma level of cytokines was analysed by ELISA kits. The results showed an increase in the expression of NEAT1, KCNQ1OT1 and RORC and a decrease in the expression of FOXP3. In plasma, an upregulation of IL17 and a downregulation of TGFB inflammatory cytokines were detected. The dysregulated expression of these genes could be attributed to relapsing‐remitting MS (RR‐MS) patients and help us understand MS pathogenesis better.
Keywords:bioinformatics  differentiation  lncRNAs  multiple sclerosis  Th17/Treg imbalances
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