Investigation of the Impact of miRNA-7151 and a Mutation in Its Target Gene lncRNA KCNQ1OT1 on the Pathogenesis of Preeclampsia

<b>Background</b>: 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 <i>KCNQ1OT1</i> and their functional contributions to PE pathogenesis. <b>Methods</b>: 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 <i>KCNQ1OT1</i> and assess their influence on trophoblast cell function and gene expression. <b>Results</b>: A bioinformatic analysis predicted a stable binding site between miR-7151-5p and <i>KCNQ1OT1</i> (minimum free energy: -37.3 kcal/mol). The dual-luciferase reporter assay demonstrated that miR-7151-5p directly targets <i>KCNQ1OT1</i>, leading to suppressed transcriptional activity. In HTR8/SVneo cells, miR-7151-5p overexpression significantly downregulated both <i>KCNQ1OT1</i> 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 <i>PLAC1</i>, <i>ANGPTL6</i>, <i>HIRA</i>, <i>GLA</i>, <i>HSF1</i>, and <i>BAG6</i>. <b>Conclusions</b>: The regulatory effect of miR-7151-5p on <i>KCNQ1OT1</i>, 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.