Quercetin inhibits invasion and promotes apoptosis of rheumatoid arthritis fibroblast-like synoviocytes by regulating miR-431-5p/mouse double minute 4 signaling pathway

Objective To investigate the effect of quercetin on invasion and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) and its molecular mechanism.

Methods Synovial tissues of 27 patients with RA and 25 patients without RA were collected. The mRNA expression and protein expression of miR-431-5p and mouse double minute 4 (MDM4) were analyzed. MiR-431-5p inhibitor, miR-NC, MDM4 overexpression vector and pcDNA 3.1 (+) vector were transfected into RA-FLSs. At 48 h after transfection, quercetin was added to each well, and cells were collected and cell viability, apoptosis rate and number of invasive cells were measured. Dual luciferase assay was used to analyze the binding relationship between miR-431-5p and MDM4.

Results The expression of miR-431-5p was significantly down-regulated in RA synovial tissue and RA-FLSs, and significantly up-regulated in quercetin induced RA-FLSS (P < 0.05). The low expression of miR-431-5p or the overexpression of MDM4 weakened the promoting effect of quercetin on apoptosis of RA-FLSs and the inhibiting effect on invasion (P < 0.05). MiR-431-5p binded MDM4 in RA-FLSs, and miR-431-5p regulated apoptosis and invasion of RA-FLSs through MDM4 (P < 0.05).

Conclusion Quercetin regulates the invasion and apoptosis of RA-FLSS by mediating miR-431-5p/MDM4 signaling pathway, suggesting that quercetin may be an alternative drug for RA.