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

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.