Wang Wuqian, Wu Xiaojia, Gu Jianmei, Chen Luan, Zhang Weihua, Sun Xiaofang, Qin Shengying, Tang Ping
Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510180, China.
Jiaxing Maternity and Children Health Care Hospital, Affiliated Women and Children Hospital Jiaxing University, Jiaxing 314051, China.
Biomedicines. 2025 Jul 24;13(8):1813. doi: 10.3390/biomedicines13081813.
: Preeclampsia (PE) is a pregnancy-specific disease and hypertensive disorder with a multifactorial pathogenesis involving complex molecular regulatory networks. Recent studies highlight the critical role of non-coding RNAs, particularly miRNAs and lncRNAs, in PE development. This study investigates the molecular interaction between miR-7151-5p and the lncRNA and their functional contributions to PE pathogenesis. : An integrative approach combining RNAhybrid-based bioinformatics, dual-luciferase reporter assays, qRT-PCR, Transwell migration and invasion assays, and RNA sequencing was employed to characterize the binding between miR-7151-5p and and assess their influence on trophoblast cell function and gene expression. : A bioinformatic analysis predicted a stable binding site between miR-7151-5p and (minimum free energy: -37.3 kcal/mol). The dual-luciferase reporter assay demonstrated that miR-7151-5p directly targets , leading to suppressed transcriptional activity. In HTR8/SVneo cells, miR-7151-5p overexpression significantly downregulated both and Notch1 mRNA, whereas its inhibition showed no significant changes, suggesting additional regulatory mechanisms of Notch1 expression. Transwell assays indicated that miR-7151-5p overexpression suppressed trophoblast cell migration and invasion, whereas its inhibition enhanced these cellular behaviors. RNA-seq analysis further revealed that miR-7151-5p overexpression altered key signaling pathways, notably the TGF-β pathway, and significantly modulates PE-associated genes, including , , , , , and . : The regulatory effect of miR-7151-5p on , along with its influence on trophoblast cell dynamics via Notch1 and TGF-β signaling pathways, highlights its role in PE pathogenesis and supports its potential as a biomarker in early PE screening.
子痫前期(PE)是一种妊娠特异性疾病和高血压疾病,其发病机制具有多因素性,涉及复杂的分子调控网络。最近的研究强调了非编码RNA,特别是miRNA和lncRNA在PE发生发展中的关键作用。本研究调查了miR-7151-5p与lncRNA之间的分子相互作用及其对PE发病机制的功能贡献。:采用基于RNAhybrid的生物信息学、双荧光素酶报告基因检测、qRT-PCR、Transwell迁移和侵袭检测以及RNA测序等综合方法,以表征miR-7151-5p与lncRNA之间的结合,并评估它们对滋养层细胞功能和基因表达的影响。:生物信息学分析预测miR-7151-5p与lncRNA之间存在稳定的结合位点(最小自由能:-37.3 kcal/mol)。双荧光素酶报告基因检测表明,miR-7151-5p直接靶向lncRNA,导致转录活性受到抑制。在HTR8/SVneo细胞中,miR-7151-5p过表达显著下调lncRNA和Notch1 mRNA,而其抑制则未显示出显著变化,提示Notch1表达存在其他调控机制。Transwell检测表明miR-7151-5p过表达抑制滋养层细胞迁移和侵袭,而其抑制则增强这些细胞行为。RNA-seq分析进一步显示,miR-7151-5p过表达改变了关键信号通路,特别是TGF-β通路,并显著调节了与PE相关的基因,包括lncRNA、Notch1、TGF-β、Smad2、Smad3和Smad7。:miR-7151-5p对lncRNA的调控作用,以及其通过Notch1和TGF-β信号通路对滋养层细胞动力学的影响,突出了其在PE发病机制中的作用,并支持其作为早期PE筛查生物标志物的潜力。