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.

中文翻译：

---

MiR‐643通过靶向TRAF6抑制脂多糖诱导的子宫内膜炎的进展

子宫内膜炎是一种常见的疾病，子宫炎症会危及女性生殖健康。MicroRNA（miRNA）在包括子宫内膜炎在内的炎性疾病中起重要作用。但是，miR-643在子宫内膜炎发展中的作用和机制尚不清楚。这项研究旨在研究miR‐643对脂多糖（LPS）诱导的炎症反应的影响，并阐明其潜在机制。培养经LPS处理的人子宫内膜上皮细胞（HEEC），以研究miR-643的体外作用。通过定量实时聚合酶链反应和蛋白质印迹分别测量miR‐643和肿瘤坏死因子受体相关因子6（TRAF6）的表达水平。LPS诱导的炎症反应通过酶联免疫吸附试验通过炎症细胞因子的分泌进行评估。免疫印迹研究了核因子κB（NF-κB）途径的激活。miR‐643与TRAF6之间的相互作用已通过生物信息学分析，荧光素酶报告基因分析和RNA免疫沉淀进行了验证。在LPS处理的HEEC中，miR‐643的表达降低，TRAF6蛋白的水平升高。miR‐643的过表达抑制LPS诱导的炎性细胞因子（肿瘤坏死因子α，白介素1β[IL-1β]和IL‐6）的分泌以及NF‐κB通路的激活。抑制TRAF6抑制了HEECs中LPS诱导的炎症反应。TRAF6被证实是miR‐643的靶标，TRAF6的修复逆转了miR‐643对LPS治疗的HEEC炎症反应的作用。通过靶向TRAF6，miR‐643共同减弱了LPS诱导的炎症反应，