Downregulation of miR‐98‐5p expression induces interleukin‐6 expression in rheumatoid fibroblast‐like synoviocytes

Abstract

The increased level of interleukin-6 (IL-6) plays a significant role in the pathogenesis of rheumatoid arthritis (RA). Specific blockade of IL-6 or its receptor has been used successfully in treating RA. MicroRNAs can regulate gene expression and act as regulators of target genes. Manipulation of specific microRNAs provides a novel therapeutic strategy for treating/preventing diseases. This study explored the role of miR-98-5p in the regulation of IL-6 expression in rheumatoid fibroblast-like synoviocytes (RA-FLSs). Real-time PCR was used to detect miR-98-5p expression in RA-FLSs and normal human fibroblast-like synovial cells (HFLSs). Site-directed gene mutagenesis and reporter gene assay were performed to identify the interaction between miR-98-5p and IL-6. Manipulation of miR-98-5p expression in RA-FLS used transfection with miR-98-5p mimic or inhibitor. Stimulation of FLSs with IL-1β induced IL-6 production. Enzyme-linked immunosorbent assay was used to detect the level of IL-6 secreted into the RA-FLS culture supernatant. Compared with HFLSs, the expression of miR-98-5p in RA-FLSs was significantly downregulated, and was negatively correlated with DAS28 scores and rheumatoid factor. In patients with anti-keratin antibody-positive RA, the expression level of miR-98-5p was lower. miR-98-5p negatively regulated the expression of IL-6 in RA-FLSs. After IL-1β stimulation, the expression of miR-98-5p decreased and the level of IL-6 protein was upregulated during IL-6 secretion. These data suggest that manipulation of miR-98-5p, which negatively modulates IL-6 expression, may be a potential clinical approach in RA.