Comprehensive bioinformatic and experimental approaches to analyze miR-200a, miR-1, and miR-548-3p expression and their targeted oxidative stress and glucose metabolic related hub genes in rheumatoid arthritis.
Source: PubMed, NCBI / U.S. National Library of Medicine
Rheumatoid arthritis is a chronic autoimmune disorder characterized by persistent synovial inflammation, oxidative stress, and metabolic reprogramming. Emerging evidence highlights miRNAs as key post-transcriptional regulators linking these pathogenic processes. Among them, miR-200a, miR-1, and miR-548-3p have been implicated in oxidative stress responses and glucose metabolism; however, their roles in RA remain largely unexplored. This study integrates bioinformatic prediction and experimental validation to examine the expression profiles of these miRNAs, identify their target genes related to oxidative stress and metabolism, and elucidate their contribution to RA pathogenesis. RT-PCR analysis revealed significant upregulation of miR-200a and downregulation of miR-1 and miR-548-3p in RA patients. RA-associated DEGs were identified from publicly available GEO microarray datasets. Further, genes linked to oxidative stress and glucose metabolism were retrieved from GeneCards and MSigDB. Overlapping genes across datasets were subjected to GO and KEGG enrichment analyses, followed by the construction of a PPI network using STRING. Five hub genes-MAPK1, FOXP1, CDC42, RUNX1, and ETS1-were identified as central nodes within the PPI network. Functional enrichment indicated their involvement in myeloid cell differentiation, regulation of apoptosis, and peptidyl-tyrosine phosphorylation, while KEGG mapping associated them with cellular senescence, circadian rhythm pathways, viral carci
Abstract
Rheumatoid arthritis is a chronic autoimmune disorder characterized by persistent synovial inflammation, oxidative stress, and metabolic reprogramming. Emerging evidence highlights miRNAs as key post-transcriptional regulators linking these pathogenic processes. Among them, miR-200a, miR-1, and miR-548-3p have been implicated in oxidative stress responses and glucose metabolism; however, their roles in RA remain largely unexplored. This study integrates bioinformatic prediction and experimental validation to examine the expression profiles of these miRNAs, identify their target genes related to oxidative stress and metabolism, and elucidate their contribution to RA pathogenesis. RT-PCR analysis revealed significant upregulation of miR-200a and downregulation of miR-1 and miR-548-3p in RA patients. RA-associated DEGs were identified from publicly available GEO microarray datasets. Further, genes linked to oxidative stress and glucose metabolism were retrieved from GeneCards and MSigDB. Overlapping genes across datasets were subjected to GO and KEGG enrichment analyses, followed by the construction of a PPI network using STRING. Five hub genes-MAPK1, FOXP1, CDC42, RUNX1, and ETS1-were identified as central nodes within the PPI network. Functional enrichment indicated their involvement in myeloid cell differentiation, regulation of apoptosis, and peptidyl-tyrosine phosphorylation, while KEGG mapping associated them with cellular senescence, circadian rhythm pathways, viral carcinogenesis, and neurotrophins signaling. Collectively, these findings suggest that miR-200a, miR-1, and miR-548-3p potentially involved in oxidative and metabolic pathways in RA, offering candidate biomarkers and therapeutic targets for disease management. Further, RT-PCR for hub genes showed elevated expression of RUNX1, MAPK1, ETS1, FOXP1, and CDC42 in RA patients. Overall, our findings reveal a potential miRNA-mediated regulatory axis underlying oxidative and metabolic disturbances in RA, offering new insights into disease mechanisms and laying the groundwork for the development of novel biomarkers and therapeutic targets.