Exploring the ceRNA Network in Multiple Sclerosis: Implications for B Cell Receptor Signaling Pathway and Therapeutic Targets

Abstract

Introduction: Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system and the second cause of disability in adults. The exact cause and pathogenic mechanisms behind this disease have not been yet understood. Besides T cells, B cells play a role in MS pathogenesis which has received less attention. Method: In the current study, the expression of long non-coding RNAs and four genes of the B cell receptor signaling pathway (CR2, BLK, BLNK, and RASGRP3) were investigated in the GSE21942 microarray dataset. Then, miRNAs targeting these genes and lncRNAs were predicted using miRWalk and DIANA-LncBase databases. Finally, the ceRNA network was constructed using desired genes, lncRNAs, and predicted miRNAs. Results: Seven differentially expressed lncRNAs were identified that all had high expression in MS patients compared with control subjects. Moreover, the expression levels of desired genes (CR2, BLK, BLNK, and RASGRP3) were upregulated in MS patients. Finally, the ceRNA network including one lncRNA (MALAT1), two predicted miRNAs (hsa-miR-92a-3p and hsa-miR-548a-3p), and three genes (CR2, RASGRP3, and BLK) was constructed. In this network, hsa-miR-92a-3p and hsa-miR-548a-3p target CR2, RASGRP3, and BLK genes, and MALAT1 constrains the effect of these miRNAs on desired genes through sponging them. Conclusion: The constructed ceRNA network can be considered a novel mechanism of MS pathogenesis and may play a key role in MS development and progression by influencing the B cell receptor signaling pathway. Furthermore, each of the components of this network can be considered a potential therapeutic target.