TRHDE gene and its plausible role in multiple sclerosis

Because of improved knowledge of mechanisms of relapsing-remitting multiple sclerosis, various disease-modifying medications have been developed during the past decades that suppress or modulate the immune system to reduce relapse rates and severity. However, the choices for treating progressive multiple sclerosis remain unsatisfactory and challenging. In this study, we employed an in silico approach using high-throughput microarray data to find dysregulated mRNA(s) and its interaction with plausible miRNA(s) in multiple sclerosis (MS) patients. Methods:The GSE۳۸۰۱۰ microarray dataset was downloaded and examined to find novel putative dysregulated mRNAs in MS patients in comparison with controls. The A↵y package was downloaded from Bioconductor. To standardize the raw data and assess differentially expressed genes (DEGs), the limma package was applied . Pathway enrichment and gene ontology (GO) analyses were performed using the Enrichr Utilizing miRWalk, a study of microRNA (miRNA)-mRNA interactions was conducted to find miRNAs for potentially dysregulated mRNAs .Results:Among the top DEGs, TRHDE gene was significantly down-regulated in the MS samples (logFC: ۵.۳۴, adj. P. Val: ۰.۰۲۳۵۳). Based on miRNA-mRNA interaction analysis, ۳ UTR of TRHDE mRNA has a significant interaction with hsa-miR-۶۰۱ (score: ۱, number of pairings: ۱۶). Enrichment analyses showed that TRHDE was involved in peptide catabolic process (GO:۰۰۴۳۱۷۱), cell-cell signaling (GO:۰۰۰۷۲۶۷), and proteolysis (GO:۰۰۰۶۵۰۸). Furthermore, TRHDE involves in metalloaminopeptidase activity (GO:۰۰۷۰۰۰۶), aminopeptidase activity (GO:۰۰۰۴۱۷۷), and pyroglutamyl-peptidase activity (GO:۰۰۱۶۹۲۰). Conclusion:There are several studies showing the role of various peptidases in MS. TRHDE may be an important potential dysregulated gene in MS patients. We postulated that miR۶۰۱ may suppress the expression level of TRHDE and modulate its peptidase activity.

کلیدواژه ها:

Microarray analysis ، Systems biology ، Multiple Sclerosis ، RNA interaction network