microRNA-614通过靶向FOXD1参与复发性流产
microRNA-614 contributes to recurrent miscarriage through targeting FOXD1
摘要
该研究基于GEO数据库筛选差异miRNA,并在135例复发性流产患者与135例健康对照中验证血浆miR-614表达及诊断效能;通过CCK-8、Transwell和双荧光素酶实验探讨其对滋养细胞增殖、侵袭、迁移及FOXD1靶向调控的作用。结果显示miR-614在RM中下调,诊断AUC为0.865,预测不良妊娠结局AUC为0.790;miR-614模拟物抑制HTR-8/JEG3细胞功能并负调控FOXD1。结论提示miR-614下调通过上调FOXD1促进RM发生。
原文摘要
OBJECTIVE: Recurrent miscarriage (RM) is a significant reproductive health issue affecting many women of childbearing age. The objective of this study was to evaluate the value of microRNA-614 (miR-614) as a potential biomarker for RM and to elucidate its functional mechanism. METHODS: Differentially expressed miRNAs (DEmiRs) were first screened from the Gene Expression Omnibus (GEO) database using a bioinformatics approach. A total of 135 patients with RM and 135 healthy controls were included. The expression levels and diagnostic performance of miR-614 were evaluated by RT-qPCR and ROC curve analysis. CCK-8 and Transwell were performed to assess the impact of the miRNA on trophoblast cell proliferation, invasion, and migration. For target gene verification, TargetScan 8.0 was utilised for prediction, followed by a luciferase activity assay to confirm direct regulation by miRNA. RESULTS: Bioinformatic interrogation of the GSE73025 dataset revealed a significant down-regulation of miR-614. Plasma miR-614 was significantly downregulated in RM patients. The area under the ROC curve (AUC) for miR-614 in distinguishing RM patients from controls was 0.865 (95% CI: 0.823-0.907, sensitivity = 77.78%, specificity = 77.78%). The AUC for predicting adverse pregnancy outcomes was 0.790 (95% CI: 0.708-0.870, sensitivity = 71.08%, specificity = 82.69%). Transfection with miR-614 mimics decreased the proliferation, invasion, and migration of HTR-8 and JEG3 cells. miR-614 Directly targets FOXD1 and negatively modulates its mRNA expression to drive RM progression. CONCLUSION: In RM patients, miR-614 is downregulated, leading to increased FOXD1 expression. miR-614 mimics suppresses trophoblast proliferation, migration, and invasion by directly targeting FOXD1. Thus, miR-614 downregulation contributes to RM pathogenesis by directly targeting FOXD1, thereby upregulating FOXD1 and inhibiting the proliferation, invasion, and migration of trophoblast cells.
推荐理由:研究提供了复发性流产的候选血浆生物标志物与FOXD1靶向机制,样本量尚可且实验验证较完整,值得关注;但诊断效能与机制结论仍需多中心、独立队列及体内实验验证。
文献解读
尚未生成。该条目分数达到自动解读阈值,下次流水线运行时会自动生成;