Dual-specificity phosphatase 5 (DUSP5) is a novel anti-inflammatory modulator in many inflammatory diseases. However, the role of DUSP5 in the fibroblast-like synoviocytes (FLS) of Rheumatoid arthritis (RA) remains unknown. In this study, we aimed to explore the biological function and regulation of DUSP5 in FLS. We found that lower DUSP5 expression levels were detected in collagen-induced arthritis (CIA) and synoviocytes MH7A. Overexpression of DUSP5 markedly decreased the proliferation,

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... ion, and invasion of MH7A, which correlated with suppressing the phosphorylation of ERK. Moreover, DUSP5 was identified as a novel target gene of miR-216a-3p, which is upregulated in FLS. Therefore, DUSP5 expression was negatively regulated by miR-216a-3p, and the effect of DUSP5 overexpression on FLS was reversed by miR-216a-3p mimics. Overall, our study demonstrates that DUSP5 is a miR-216a-3p target gene and its anti-inflammatory function in FLS via inactivation of ERK. These results revealed that the miR-216a-3p/DUSP5 pathway may play a crucial role in the malignant behavior of FLS, which may serve as a new target for the treatment of RA.