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

Abstract

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‐κB (NF‐κB) 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‐α, interleukin‐1β [IL‐1β], and IL‐6) and activation of NF‐κB 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.

The relationship between TRAF6 and tumors

“…Evidences also confirmed that miR-146b-5p is tumor suppressor by inhibiting the TRAF6/p-Akt signaling pathway in vitro and in vivo [77]. miR-643 has recently been proved to targeting TRAF6 in human endometrial epithelial cells (HEECs) that significantly reduces the expression of TRAF6 [78]. miR-124 has also been reported to be related to negative regulation of TRAF6 expression in human osteosarcoma cells and colorectal cancer cells [79,80].…”

microRNAs in female infertility: An overview

“…90 Studies revealed that miR-643 expression is reduced in lipopolysaccharide-induced endometritis and a high level of miR-643 expression reduces inflammation in those tissues. 86 The lower level of miR-488 expression in lipopolysaccharide induces inflammation of the endometrium. On the other hand, this miRNA suppresses inflammatory cytokines production in BEND cells.…”

Endometrial causes of recurrent pregnancy losses: endometriosis, adenomyosis, and chronic endometritis

“…Also, TRAF6, a validated target of miR-643 and TRAF6 restoration, reversed the effects of miR-643 on inflammation response in LPS-treated human endometrial epithelial cells. Collectively, miR-643 attenuated LPS-induced inflammatory response by targeting TRAF6, indicating a novel avenue for treating CE (156).…”