From Pathways to Therapies: The Roles of Ubiquitination and MAPK Signalling in Rheumatoid Arthritis

Abstract

Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder that causes joint damage and disability. The complexity of its pathogenesis involves multiple signaling pathways, including ubiquitination and MAPK (Mitogen-Activated Protein Kinase) pathways.

Objective: This study investigates the mechanistic involvement of ubiquitination and MAPK signalling in RA, aiming to identify potential biomarkers and therapeutic targets.

Methods: Differentially expressed genes (DEGs) related to ubiquitination were obtained from the GEO database. Functional enrichment and protein–protein interaction (PPI) network analyses were performed. A nomogram prediction model was constructed and externally validated. RT-qPCR was conducted using RA patient samples for experimental validation.

Results: Fifteen ubiquitination-related DEGs were identified. Enrichment analysis showed a significant association with the MAPK pathway. Key genes such as TRIM25, TRAF6, and UBE2N were highlighted in the PPI network. The nomogram demonstrated strong predictive performance, and elevated gene expression levels were confirmed in clinical samples.

Conclusion: Ubiquitination and MAPK signalling play essential roles in RA pathogenesis. The identified genes may serve as novel biomarkers and targets for treatment strategies in RA.