Downregulated MYL1 Emerges as a Promising Diagnostic Biomarker for Rheumatoid Arthritis

Area of Science:

• * Molecular biology
• * Immunology
• * Rheumatology

Background:

• * Rheumatoid arthritis (RA) is a chronic autoimmune disease impacting millions globally, characterized by joint pain and inflammation.
• * The precise pathogenesis and effective management of RA remain challenging due to incomplete understanding.
• * The role of Myosin light chain 1 (MYL1), a muscle regulatory protein, in RA pathogenesis is currently unknown.

Purpose of the Study:

• * To investigate the role of Myosin light chain 1 (MYL1) in the pathogenesis of rheumatoid arthritis (RA).
• * To identify MYL1 as a potential diagnostic biomarker for RA.
• * To explore the functional and mechanistic implications of MYL1 dysregulation in RA.

Main Methods:

• * Transcriptomic data from RA patients and healthy controls were analyzed using LASSO regression and random forest to identify differentially expressed genes (DEGs).
• * Diagnostic performance was evaluated using Receiver Operating Characteristic (ROC) curves and Area Under the Curve (AUC).
• * Functional enrichment, immune-infiltration analyses (CIBERSORT), qRT-PCR, and Western blotting were employed to explore mechanisms and validate findings in a rat RA model.

Main Results:

• * MYL1 was found to be significantly downregulated in RA patients, exhibiting high diagnostic value (AUC > 0.8).
• * Functional enrichment analysis indicated MYL1's involvement in muscle structure development, immune regulation, and calcium signaling pathways.
• * Validation in a rat RA model confirmed reduced MYL1 expression at both mRNA and protein levels, consistent with human data, and revealed associations with regulatory T cells, activated NK cells, and M1 macrophages.

Conclusions:

• * MYL1 is consistently downregulated in RA and shows potential as a diagnostic biomarker.
• * MYL1 may contribute to RA pathology via calcium signaling, muscle function, and immune cell regulation.
• * Further clinical and mechanistic studies are warranted to fully elucidate MYL1's role in RA.