BACKGROUND Pre-eclampsia (PE) is regarded as the leading cause of maternal and neonatal morbidity and mortality. Nevertheless, the potential mechanism for the regulation of trophoblast behaviors and the pathogenesis of PE remain largely elusive. Recently, accumulating evidence emphasized that aberrant expression of long non-coding RNAs (lncRNAs) functions as imperative regulators in human diseases, including PE. Thus, identifying PE-related specific lncRNAs to uncover the underlying molecular mechanism is of much significance. However, the functional roles and underlying mechanisms of lncRNAs in PE progression remain unclear. METHOD Placenta tissues obtained from patients with PE and healthy pregnant women were performed to measure TUG1 expression by qRT-PCR analysis. Transient transfections were conducted to alter TUG1 expression. Cell Counting Kit-8 (CCK-8) and flow cytometry assays were carried out to assess cell proliferation and apoptosis, respectively. Transwell and tube formation assays were performed to measure the capacity of cell invasion and angiogenesis. Moreover, the luciferase reporter assay was subjected to verify the binding relationship between TUG1 and miR-29b. Western blot analysis was performed to detect the expression of key proteins in the PI3K/AKT and ERK pathway. RESULTS Here, we identified a lncRNA, TUG1, which was notably decreased in placental samples of PE patients. Functional experiments of loss- or gain-of-function assays also verified that ectopic expression of TUG1 promoted cell proliferation, invasion, and angiogenesis, but negatively regulated cell apoptosis, whereas TUG1 inhibition presented the opposite effects. Furthermore, mechanistic researches revealed that TUG1 could act as a molecular sponge for miR-29b, thus regulating MCL1, VEGFA, and MMP2 to modulate PE development. CONCLUSIONS Taken together, our findings demonstrated that TUG1 exerts as a critical role in PE progression, which might furnish a novel therapeutic marker for PE treatment.

中文翻译：

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lncRNA TUG1 通过靶向滋养层细胞中的 miR-29b 来调节增殖、凋亡、侵袭和血管生成。

背景先兆子痫（PE）被认为是孕产妇和新生儿发病和死亡的主要原因。然而，调节滋养层行为和 PE 发病机制的潜在机制在很大程度上仍不清楚。最近，越来越多的证据强调，长非编码 RNA (lncRNA) 的异常表达在包括 PE 在内的人类疾病中发挥着重要的调节作用。因此，鉴定PE相关的特异性lncRNA以揭示潜在的分子机制具有重要意义。然而，lncRNA 在 PE 进展中的功能作用和潜在机制仍不清楚。方法 取自PE患者和健康孕妇的胎盘组织，通过qRT-PCR分析测量TUG1表达。进行瞬时转染以改变 TUG1 表达。进行细胞计数试剂盒-8 (CCK-8) 和流式细胞术测定分别评估细胞增殖和凋亡。进行Transwell和管形成测定来测量细胞侵袭和血管生成的能力。此外，通过荧光素酶报告基因测定验证了TUG1和miR-29b之间的结合关系。进行Western blot分析检测PI3K/AKT和ERK通路中关键蛋白的表达。结果在这里，我们鉴定了一种 lncRNA，即 TUG1，它在 PE 患者的胎盘样本中显着减少。功能丧失或获得功能实验也证实，TUG1的异位表达促进细胞增殖、侵袭和血管生成，但负向调节细胞凋亡，而TUG1抑制则呈现相反的效果。此外，机制研究表明，TUG1 可以充当 miR-29b 的分子海绵，从而调节 MCL1、VEGFA 和 MMP2 来调节 PE 的发展。结论 综上所述，我们的研究结果表明 TUG1 在 PE 进展中发挥着关键作用，这可能为 PE 治疗提供一种新的治疗标志物。