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 miR-125b 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-κB (IκB)-α or corresponding controls, and then stimulated with LPS or incubated with nuclear factor kappa B (NF-κB) inhibitors pyrrolidine dithiocarbamate (PDTC). The effects of miR-125b abnormal expression on pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β and NF-κB pathway key factors phospho-p65 (p-p65) and IκB-α were assessed. Pearson correlation analysis was performed to assess the relationship between miR-125b expression and pro-inflammatory 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-α, IL-6, IL-1β and p-p65 (P<0.05 or P<0.01), but markedly decreased IκB-α (P<0.05). Contrary results were obtained by miR-125b downregulation. Additionally, there were strong positive relationships between miR-125b and TNF-α (R2 =0.7569, P<0.000), IL-6 (R2 =0.8479, P<0.000), and IL-1β (R2 =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-IκB-α (P<0.01). In conclusion, our results suggest that elevated miR-125b promotes inflammation in RA by activation of NF-κB pathway.