Man Chen, Fang Zong, Jingjing Zhang, Yaxuan Wang, Baoheng Xing
Downregulated miR-498 aggravates endothelial dysfunction and facilitates GH progression via inhibiting PTEN/AKT signaling. This study identifies circulating miR-498 as a promising non-invasive diagnostic biomarker and reveals a vascular-specific regulatory axis for GH.
BACKGROUND: Gestational hypertension (GH) remains a major cause of maternal and fetal morbidity. miR-498 has been implicated in vascular dysfunction, yet its role and mechanism in GH remain unclear.
METHODS: Clinical serum samples from 106 GH patients and 82 healthy pregnant controls were collected to detect circulating miR-498 expression and analyze its correlation with clinical parameters. The dual-luciferase reporter assay was applied to confirm the direct binding between miR-498 and PTEN. All in vitro functional experiments, including CCK-8 proliferation assay, Transwell migration and invasion assays, were conducted exclusively in HUVECs.
RESULTS: Hsa-miR-498-5p (miR-498) was significantly downregulated in serum of GH patients and presented favorable diagnostic performance. Circulating miR-498 levels were negatively correlated with systolic blood pressure and neonatal birth weight, while positively correlated with gestational age. Mechanistically, miR-498 directly targeted PTEN. miR-498 overexpression enhanced the proliferative, migratory and invasive capacities of HUVECs, and ectopic PTEN overexpression could reverse these cellular phenotypes.
CONCLUSION: Downregulated miR-498 aggravates endothelial dysfunction and facilitates GH progression via inhibiting PTEN/AKT signaling. This study identifies circulating miR-498 as a promising non-invasive diagnostic biomarker and reveals a vascular-specific regulatory axis for GH.