miR-410-3p acts as an oncogene or a tumor suppressor in some malignancies. However, its role in rheumatoid arthritis (RA) is unknown. The study was conducted to investigate the effect of miR-410-3p on the pathogenesis of RA. Real-time RT-PCR was used to determine the mRNA levels of miR-410-3p in synovial tissues and fibroblast-like synoviocytes (FLSs). An ELISA was performed to examine the production levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and matrix metalloproteinase (MMP)-9. Western blotting was conducted to determine the protein levels of IκB-α, p-IκBα, p65, and p-p65. Nuclear factor (NF)-κB activation and nuclear translocation assays were performed to confirm the activation of NF-κB. We found that the expression level of miR-410-3p was downregulated in synovial tissues and FLSs from RA. Overexpression of miR-410-3p significantly reduced the secretion of TNF-α, IL-1β, IL-6, and MMP-9 in human RA fibroblast-like synoviocytes (HFLS-RA); whereas miR-410-3p inhibition increased the expression levels of these cytokines. Furthermore, miR-410-3p suppresses the activation of NF-κB signaling pathway. Moreover, NF-κB inhibitor restored the elevation of TNF-α, IL-1β, IL-6, and MMP-9 induced by miR-410-3p inhibition. Our results demonstrate that miR-410-3p acts an inflammatory suppressor in the pathogenesis of RA by regulating the NF-κB signaling pathway. These data suggest a novel function of miR-410-3p and provide insight into the complex mechanisms involved in RA.
Keywords: NF-κB signaling; cytokines; fibroblast-like synoviocytes; miR-410-3p; rheumatoid arthritis.