Elevated microRNA-125b promotes inflammation in rheumatoid arthritis by activation of NF-κB pathway

microRNA-125b(miR-125b) has been reported to be increased in rheumatoid arthritis (RA). However, the role of miR-125b in RA remains to be fully elucidated. We aimed to explore the functional role of miR125b in RA, as well as the underlying mechanism. The expression of miR-125b in serum and synovial tissues of patients with RA and healthy controls was confirmed. In addition, the levels of miR-125b in lipopolysaccharide (LPS)-stimulated fibroblast-like synoviocytes (FLS) were also measured. FLS were transfected with miR-125b mimic, antisense oligonucleotides (ASO)-miR-125b, pcDNA-inhibitor of NF kappa B (I kappa B)-a or corresponding controls, and then stimulated with LPS or incubated with nuclear factor kappa B (NF-kappa B) inhibitors pyrrolidine dithiocarbamate (PDTC). The effects of miR-125b abnormal expression on pro- inflammatory cytokines including tumor necrosis factor (TNF)-alpha, interleukin (IL)- 6 and IL-1 beta and NF-kappa B pathway key factors phospho-p65 (p-p65) and I kappa B- a were assessed. Pearson correlation analysis was performed to assess the relationship between miR-125b expression and proinflammatory cytokines expression. Result showed that, the levels of miR-125b were significantly increased in RA serum and synovial tissues, as well as in LPS- stimulated FLS (P < 0.01). miR-125b overexpression statistically increased the expression of TNF- a, IL-6, IL-1 beta and p-p65 (P < 0.05 or P < 0.01), but markedly decreased I kappa B-a (P < 0.05). Contrary results were obtained by miR-125b downregulation. Additionally, there were strong positive relationships between miR-125b and TNF-a (R-2 = 0.7569, P < 0.000), IL-6 (R-2 = 0.8479, P < 0.000), and IL-1 beta (R-2 = 0.8037, P < 0.000). Moreover, the upregulated levels of pro- inflammatory cytokines were markedly decreased by PDTC (P < 0.01) and further downregulated by co-transfection with pcDNA-I kappa B-a (P < 0.01). In conclusion, our results suggest that elevated miR- 125b promotes inflammation in RA by activation of NF-kappa B pathway. (C) 2017 Elsevier Masson SAS. All rights reserved.