RGS2-related non-coding interaction network modulates the NF-Kappa B signaling pathway in MS patients: a systems biology investigation

Background: Multiple Sclerosis (MS) is recognized as the most prevalent chronic inflammatory condition that targets the brain and spinal cord. According to the third edition of the Atlas of MS, around 2.8 million individuals worldwide are affected by Multiple Sclerosis, equating to a prevalence of 35.9 cases per 100,000 people. In this study, we evaluated the expression levels of potential biomarkers in a high-throughput MS dataset to find novel highly dysregulated RNAs in MS patients. Furthermore, a novel RNA regulatory network has been visualized to find new non-coding interaction patterns in the MS-related signaling pathways. Methods: Using R Studio, high-throughput gene expression MS datasets were analyzed to find highly dysregulated mRNAs in MS patients. miRNA, lncRNA, and protein interaction analyses were conducted by miRWalk and lncRRIsearch databases. Using visualized interaction networks, pathway enrichment analysis was performed using Enrichr and KEGG. qRT-PCR experiment was performed for the validation of gene expression analyses. 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. Conclusion: 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.