SummaryPreeclampsia (PE), a pregnancy-specific disease, has become one of the leading causes of maternal and neonatal morbidity and mortality. Pathogenesis of PE has still not been fully addressed and there is a great need to develop early diagnosis markers and effective therapy. This study aimed to determine if lncRNA SNHG14 has a protective effect on placental trophoblast and prevents PE. SNHG14 levels in the peripheral blood from patients with PE or from women with healthy pregnancies were detected using RT-qPCR. The relationship between SNHG14 and miR-330-5p was determined using a dual-luciferase reporter assay. In addition, cell proliferation and cell cycle were evaluated by performing CCK8 assays and flow-cytometric analysis, respectively. Wound-healing and transwell assays were performed to assess cell migration and invasion ability. lncRNA SNHG14 was downregulated in PE patients; it was involved in trophoblast proliferation and regulated cell proliferation during G1/S transition. In addition, lncRNA SNHG14 promoted migration, invasion and epithelial–mesenchymal transition (EMT) in HTR-8/SVneo cells. Luciferase reporter assay indicated that lncRNA SNHG14 served as a molecular sponge for miR-330-5p and negatively regulated miR-330-5p expression in PE. Furthermore, the effects of silenced SNHG14 on trophoblast proliferation, migration, invasion and EMT were reversed by addition of miR-330-5p inhibitor, suggesting that in PE lncRNA SNHG14 functions by competitively binding to miR-330-5p. Taken together, the current study demonstrated that in PE lncRNA SNHG14 is a vital regulator by binding to miR-330-5p. SNHG14 might serve as a therapeutic application in PE progression.

中文翻译：

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lncRNA SNHG14 通过靶向 miR-330-5p 在先兆子痫中参与滋养层细胞增殖、迁移、侵袭和上皮-间质转化

摘要先兆子痫 (PE) 是一种妊娠特异性疾病，已成为孕产妇和新生儿发病率和死亡率的主要原因之一。PE 的发病机制仍未完全阐明，亟需开发早期诊断标志物和有效治疗方法。本研究旨在确定 lncRNA SNHG14 是否对胎盘滋养层具有保护作用并预防 PE。使用 RT-qPCR 检测 PE 患者或健康妊娠妇女外周血中的 SNHG14 水平。SNHG14 和 miR-330-5p 之间的关系使用双荧光素酶报告基因测定法确定。此外，分别通过进行 CCK8 测定和流式细胞术分析来评估细胞增殖和细胞周期。进行伤口愈合和 transwell 测定以评估细胞迁移和侵袭能力。lncRNA SNHG14 在 PE 患者中下调；它参与 G1/S 过渡期间的滋养层增殖和调节细胞增殖。此外，lncRNA SNHG14 促进 HTR-8/SVneo 细胞的迁移、侵袭和上皮间质转化 (EMT)。荧光素酶报告基因分析表明，lncRNA SNHG14 作为 miR-330-5p 的分子海绵并负调控 PE 中 miR-330-5p 的表达。此外，通过添加 miR-330-5p 抑制剂，沉默的 SNHG14 对滋养层增殖、迁移、侵袭和 EMT 的影响被逆转，这表明在 PE lncRNA 中，SNHG14 通过竞争性结合 miR-330-5p 发挥作用。总之，目前的研究表明，在 PE lncRNA 中，SNHG14 通过与 miR-330-5p 结合是一种重要的调节因子。SNHG14 可作为 PE 进展的治疗应用。