The effects of miR-26b-5p on fibroblast-like synovial cells in rheumatoid arthritis (RA-FLS) via targeting EZH2.

Abstract Objective To study the possible effects of miR-26b-5p on fibroblast-like synovial cells in rheumatoid arthritis (RA-FLS) through targeting enhancer of zeste homolog 2 (EZH2). Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect miR-26b-5p and EZH2 expressions in synovial tissues of RA patients and healthy controls. Dual luciferase reporter assay was adopted to verify the targeting relationship between miR-26b-5p and EZH2. RA-FLS was divided into Blank, mimics NC, mimics, NC siRNA, EZH2 siRNA and inhibitors + EZH2 siRNA groups, followed by the assessment of proliferation, apoptosis, migration and invasion. The expression of genes and proteins in RA-FLS was tested by qRT-PCR and western blotting, respectively. Results MiR-26b-5p expression was lower, while EZH2 expression was higher in synovial tissue of RA patients than healthy controls; and miR-26b-5p was negatively correlated with the EZH2 in synovial tissue of RA patients, which were both related with disease activities. MiR-26b-5p can target EZH2 in RA-FLS. In vitro, miR-26b-5p mimics down-regulated EZH2 expression in RA-FLS. Compared with EZH2 siRNA group, the miR-26b-5p expression in inhibitors + EZH2 siRNA group was reduced, but EZH2 expression was increased. EZH2 siRNA inhibited the proliferation, invasion and migration of RA-FLS, promoted cell apoptosis, and inhibited the expression of TNF-α, IL-1β, IL-6, IL-17, MMP-2, MMP-9, which were reversed by miR-26b-5p inhibitor. Conclusion MiR-26b-5p may affect the biological characteristics of RA-FLS via targeting EZH2, including proliferation, apoptosis, invasion and migration, as well as the secretion of cytokines, thus playing a potential therapeutic role in RA.