The aim of this study was to investigate the role of ubiquitin-specific peptidase 8 (USP8) in human trophoblast cells and its molecular mechanism. Based on the GSE30186 dataset, USP8 was identified as a downregulated gene in pre-eclampsia (PE). Analysis of clinical samples also revealed that USP8 expression at both the mRNA and protein levels in placental tissue from patients with PE was significantly lower than that from healthy pregnant women. Plate clone formation, scratch-wound healing, Transwell, tubule formation, and western blot assays collectively revealed that USP8 overexpression promoted the proliferation, migration, invasion, and pro-angiogenesis function of trophoblast cells, while USP8 knockdown induced the opposite effects. Bioinformatics analysis and luciferase reporter assay results indicated that the 3′ untranslated region of USP8 was targeted by miR-874-3p. USP8 expression in the placental tissue of patients with PE was significantly lower than that of healthy pregnant women. USP8 actively regulated the growth and invasion of human trophoblast cells and stabilized the epithelial sodium channel (ENaC) on the cell membrane. MiR-874 targeted USP8 in the trophoblast cells and upregulation of miR-874-3p resulted in a decrease in the proliferation, migration, invasion, and pro-angiogenesis ability of trophoblast cells. These results indicate that USP8 can reverse the above mentioned negative effects of miR-874-3p on trophoblast cells. USP8 targeted by miR-874-3p facilitates the invasion of trophoblastic cells by stabilizing the expression of the ENaC, which may be a possible therapeutic target for PE.

本研究旨在探讨泛素特异性肽酶8（USP8）在人滋养层细胞中的作用及其分子机制。基于 GSE30186 数据集，USP8 被确定为先兆子痫 (PE) 中的下调基因。对临床样本的分析还显示，PE患者胎盘组织中USP8的mRNA和蛋白水平表达均显着低于健康孕妇。板克隆形成、划痕伤口愈合、Transwell、肾小管形成和蛋白质印迹测定共同表明，USP8过表达促进滋养层细胞的增殖、迁移、侵袭和促血管生成功能，而USP8敲低则诱导相反的作用。生物信息学分析和荧光素酶报告基因检测结果表明，USP8 的 3' 非翻译区是 miR-874-3p 的靶标。PE患者胎盘组织中USP8的表达量显着低于健康孕妇。USP8积极调节人滋养层细胞的生长和侵袭，并稳定细胞膜上的上皮钠通道（ENaC）。miR-874 靶向滋养层细胞中的 USP8，上调 miR-874-3p 导致滋养层细胞的增殖、迁移、侵袭和促血管生成能力下降。这些结果表明USP8可以逆转miR-874-3p对滋养层细胞的上述负面影响。miR-874-3p靶向的USP8通过稳定ENaC的表达来促进滋养层细胞的侵袭，这可能是PE的可能治疗靶点。