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 protein10 (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.