Comprehensive analysis and validation of autophagy-related gene in rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease in which autophagy is pivotal in its pathogenesis. This study aims to identify autophagy-related genes associated with RA and investigate their functional roles.

Methods: We performed mRNA sequencing to identify differentially expressed genes (DEGs) between RA and osteoarthritis (OA) and intersected these with autophagy-related genes to obtain autophagy-related DEGs (ARDEGs) in RA. Bioinformatics and machine learning approaches were used to identify key biomarkers. Functional experiments, including real-time cellular analysis (RTCA), scratch healing, and flow cytometry, were conducted to examine the effects of gene silencing on the proliferation and migration of MH7A cells.

Results: A total of 37 ARDEGs were identified in RA. Through bioinformatics analysis, interferon regulatory factor 4 (IRF4) emerged as a key hub gene, with its high expression confirmed in RA synovial tissues and RA FLS cells. IRF4 knockdown inhibited the proliferation and migration and promoted the death of MH7A cells.

Conclusion: IRF4 is an autophagy-related diagnostic biomarker for RA. Targeting IRF4 could serve as a potential diagnostic and therapeutic strategy for RA, although further clinical studies are required to validate its effectiveness.