Abstract
Preeclampsia (PE) is a pregnancy-specific disorder characterized by new-onset hypertension after 20 weeks of gestation, and is associated with abnormal placental development, placental ischemia, and systemic endothelial dysfunction. There is new evidence that ferroptosis, a kind of cell death that depends on iron, plays a role in placental injury in PE. Unfortunately, our understanding of the regulatory mechanisms that underlie ferroptosis in PE is still limited. The purpose of this research was to examine miR-150-3p's function as a diagnostic biomarker and its function in controlling ferroptosis in the placenta of patients with PE via modulating ferritin heavy chain 1 (FTH1). We compared clinical indicators and placental ferroptosis markers in PE and normal pregnant women. Bioinformatics tools were used to predict miRNAs targeting ferroptosis-related genes, and experimental validation was performed in placental tissues and trophoblast cells. Dual-luciferase reporter assays and cell function analyses were conducted to examine the role of miR-150-3p and its target FTH1. PE placentas exhibited increased iron content and reduced expression of GPX4, SLC7A11, and FTH1. Bioinformatics identified miR-150-3p, miR-27a-3p, and miR-214-3p as top regulators of FTH1, SLC7A11, and GPX4, respectively. MiR-150-3p was markedly upregulated in PE and showed high diagnostic accuracy (AUC = 0.868). Functional assays revealed that miR-150-3p promotes ferroptosis in trophoblast cells by directly downregulating FTH1, leading to increased iron accumulation, lipid peroxidation, and oxidative stress. Our findings reveal a novel molecular pathway involving miR-150-3p/FTH1 in the development of PE, offering insights into potential biomarkers and therapeutic strategies targeting ferroptosis.