MiR-152 inhibits rheumatoid arthritis synovial fibroblast proliferation and induces apoptosis by targeting ADAM10

Abstract

miR-152 has been reported to be downregulated in rheumatoid arthritis (RA). However, the functional significance and molecular mechanisms underlying the role of miR-152 in RA remain largely unknown. The present study aimed to explore the functional role and the underlying mechanisms of miR-152 in RA. The expression of miR-152 in serum, synovial tissues, and fibroblast-like synoviocytes (FLS) from patients with RA and healthy controls was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, cell cycle phase distribution and apoptosis of FLS were measured by Cell Counting Kit-8 and flow cytometry assays. The effects of miR-152 on the production of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-8, were examined by ELISA. The target gene of miR-152 was discovered by miRNA-target prediction bioinformatics analysis, and confirmed by dual-luciferase reporter assay, RT-qPCR and western blotting. Spearman's correlation analysis was performed to assess the relationship between miR-152 expression and a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10). The results demonstrated that miR-152 expression levels were significantly decreased in RA serum, synovial tissues and RA-FLS compared with healthy controls. Overexpression of miR-152 significantly inhibited cell proliferation, promoted cell apoptosis, and decreased TNF-α, IL-1β, IL-6 and IL-8 production in RA-FLS cells. Additionally, ADAM10 was demonstrated to be a target of miR-152, and expression of the two genes was significantly negatively correlated. Of note, restoration of ADAM10 expression partially reversed the effects of miR-152 on cell proliferation and apoptosis in RA-FLS. Thus, miR-152 may serve as a potential target for therapeutic intervention in RA.