MiR-643 inhibits lipopolysaccharide-induced endometritis progression by targeting TRAF6

Endometritis is a prevalent disease with inflammation of uterus endangering women reproductive health. MicroRNAs (miRNAs) play important roles in inflammatory disorders, including endometritis. However, the role and mechanism of miR-643 in endometritis development remain unclear. This study aimed to investigate the effect of miR-643 on lipopolysaccharide (LPS)-induced inflammatory response and clarify the potential mechanism. LPS-treated human endometrial epithelial cells (HEECs) were cultured to investigate the role of miR-643 in vitro. The expression levels of miR-643 and tumor necrosis factor receptor-associated factor 6 (TRAF6) were measured via quantitative real-time polymerase chain reaction and western blot, respectively. LPS-induced inflammatory response was assessed by inflammatory cytokines secretion via enzyme-linked immunosorbent assay. The activation of nuclear factor-kappa B (NF-kappa B) pathway was investigated by western blot. The interaction between miR-643 and TRAF6 was validated by bioinformatics analysis, luciferase reporter assay, and RNA immunoprecipitation. The expression of miR-643 was decreased and TRAF6 protein level was enhanced in LPS-treated HEECs. The overexpression of miR-643 suppressed LPS-induced secretion of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta [IL-1 beta], and IL-6) and activation of NF-kappa B pathway. The knockdown of TRAF6 inhibited LPS-induced inflammatory response in HEECs. TRAF6 was validated as a target of miR-643 and TRAF6 restoration reversed the effect of miR-643 on inflammation response in LPS-treated HEECs. Collectively, miR-643 attenuated LPS-induced inflammatory response by targeting TRAF6, indicating a novel avenue for the treatment of endometritis.