Evaluation of hsa-miR-146a-5p and hsa-miR-155-5p as candidate biomarkers for early detection of rheumatoid arthritis in Mexican postmenopausal women

Abstract

Introduction: Rheumatoid arthritis is a chronic systemic autoimmune and inflammatory disease characterized by progressive joint damage, pain, stiffness, and functional limitation, which negatively affect quality of life. Its etiology is multifactorial and involves genetic, environmental, and immunological factors. Early diagnosis remains a clinical challenge because initial manifestations may be nonspecific and currently available biomarkers may not provide sufficient sensitivity and specificity during early disease stages. In this context, microRNAs have emerged as promising molecular tools because they regulate gene expression at the post-transcriptional level and participate in key biological processes, including apoptosis, cell differentiation, proliferation, and immune response regulation. In particular, hsa-miR-146a-5p and hsa-miR-155-5p have been identified as important regulators of inflammatory and immune pathways involved in rheumatoid arthritis pathophysiology.

Objective: To evaluate the expression of hsa-miR-146a-5p and hsa-miR-155-5p in Mexican postmenopausal women with rheumatoid arthritis and compare their expression with that of healthy women, in order to explore their potential as complementary molecular biomarkers for early disease detection.

Methodology: Public gene expression databases were used to identify rheumatoid arthritis-associated microRNAs, target genes, and biological pathways related to changes in microRNA expression. Functional enrichment analyses were performed to characterize the biological relevance of identified targets. These analyses focused on immune and inflammatory processes associated with rheumatoid arthritis, including B-cell receptor signaling, apoptosis, inflammatory response, Fc receptor-mediated signaling, and other immune-related pathways. Experimental validation will be performed using RT-qPCR, a highly sensitive and specific technique for microRNA quantification. Peripheral blood samples will be obtained from women with rheumatoid arthritis and healthy controls.

Results: The in-silico analysis identified differential expression patterns for hsa-miR-146a-5p and hsa-miR-155-5p between rheumatoid arthritis and control groups. A total of 113 target genes associated with rheumatoid arthritis were identified. Among these, JUN, PIK3R1, KRAS, and CBL were highlighted because of their participation in inflammatory signaling, immune activation, cell proliferation, and cell survival pathways.

Preliminary conclusions: The findings suggest that hsa-miR-146a-5p and hsa-miR-155-5p are biologically plausible candidate molecular biomarkers for rheumatoid arthritis. The identification of rheumatoid arthritis-associated target genes and enriched immune pathways supports their potential contribution to early disease detection. Future RT-qPCR validation in peripheral blood samples will be necessary to confirm their diagnostic utility in Mexican postmenopausal women.