MiR-1193 represses the proliferation and induces the apoptosis of interleukin-1-treated fibroblast-like synoviocytes via targeting JAK3

Objectives: To explore the roles of miR-1193/Janus kinase 3 (JAK3) axis and the potential mechanism in rheumatoid arthritis (RA). Methods: The dysregulated genes and microRNAs (miRNAs) were screened using the datasets of and , while the upstream miRNA of JAK3 was forecasted by TargetScan. Then the MH7A cells were treated with interleukin-1 beta (IL-1 beta) to induce local inflammation. Double luciferase report assay was used to estimate the association between JAK3 and miR-1193. Flow cytometry and 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assays were taken to analyze the apoptosis and proliferation of MH7A cells with IL-1 beta-induced inflammation, respectively. The relative expression of genes and proteins were detected by quantitative real-time polymerase chain reaction and western blot analyses. Finally, rescue experiments were employed to explore the effects of miR-1193/JAK3 axis on IL-1 beta-induced inflammation. Results: JAK3 was notably up-regulated in RA, and was targeted and negatively regulated by miR-1193 which was lowly expressed in RA tissues and IL-1 beta-treated cells. MiR-1193 mimic significantly inhibited while miR-1193 inhibitor promoted the proliferation of MH7A cells with IL-1 beta-induced inflammation. Furthermore, overexpression of JAK3 presented auxo-action while depletion of JAK3 exhibited inhibitory effect on the proliferation of MH7A cells with IL-1 beta-induced inflammation, which could be weakened by miR-1193 mimic and miR-1193 inhibitor, respectively. Analogously, JAK3 recovered the cell proliferation that inhibited by miR-1193 mimic and inhibited cell apoptosis enhanced by miR-1193 mimic. Conclusion: Up-regulation of miR-1193 suppressed the proliferation and expedited the apoptosis of MH7A cells with IL-1 beta-induced inflammation through targeting JAK3, which might provide novel understanding on the mechanism underlying RA.