Abstract
PURPOSE: Rheumatoid arthritis (RA) affects millions of people worldwide and causes chronic joint pain with incompletely understood pathogenesis and challenging management. Myosin light chain 1 (MYL1) a muscle regulatory protein, has an unknown role in RA pathogenesis. METHODS: We analyzed transcriptomic data from RA patients and healthy controls in the Gene Expression Omnibus (GEO). Using least absolute shrinkage and selection operator (LASSO) regression and random forest, we identified differentially expressed genes (DEGs). Diagnostic performance was assessed using receiver operating characteristic (ROC) curves and area under the curve (AUC). To explore potential mechanisms, we conducted functional enrichment and immune-infiltration analyses. We further validated MYL1 expression in a rat RA model using qRT-PCR and Western blotting. RESULTS: We found MYL1 significantly downregulated in RA with high diagnostic value (AUC > 0.8). Enrichment analyses revealed its involvement in muscle structure development, immune regulation, and calcium signaling pathways. CIBERSORT analysis indicated associations with immune cell infiltration, particularly regulatory T cells, activated natural killer (NK) cells, and M1 macrophages. The rat model confirmed reduced MYL1 expression at both mRNA (p < 0.001) and protein (p = 0.009) levels, consistent with human data. CONCLUSION: MYL1 is consistently downregulated in RA and may serve as a potential diagnostic biomarker. The results indicate that MYL1 may be involved in the pathological process of RA through calcium signaling, muscle function, and immune cell regulation. However, further clinical and mechanistic studies are warranted.