Li Xuexiang, Liu Zhiqiang, Shan Guilian, Shi Lili, Liu Zhihua
Department of Neonatology, Shengli Oilfield Central Hospital, Dongying, Shandong, China.
Front Pediatr. 2025 Sep 9;13:1654832. doi: 10.3389/fped.2025.1654832. eCollection 2025.
Neonatal Sepsis (NS) is an important cause of neonatal death, often accompanied by acute lung injury (ALI). Ferroptosis plays a role in infectious diseases, but its regulatory mechanism in NS-related ALI remains unclear. The aim of this study is to investigate the mechanism of EMX2OS in promoting ferroptosis in ALI.
The expression level of EMX2OS in peripheral blood of patients with NS and its diagnostic value were detected by clinical samples. LPS-induced A549 cells were used to establish an ALI model. The targeting relationship between EMX2OS, miR-654-3p and AKT3 was verified by qRT-PCR, CCK-8, detection kit and dual-luciferase assays, and the cell viability and ferroptosis level were evaluated.
EMX2OS was highly expressed in NS and served as a potential diagnostic marker. In LPS-induced lung injury model, high expression of EMX2OS decreased cell viability and enhanced ferroptosis. Silencing EMX2OS had the opposite effects. EMX2OS regulated cell viability and ferroptosis through miR-654-3p/AKT3 axis.
This study reveals for the first time that EMX2OS serves as a diagnostic marker for NS and promotes ferroptosis through miR-654-3p/AKT3 axis, thereby exacerbating lung injury. EMX2OS to regulate ferroptosis may become potential therapeutic strategies for lung injury.
新生儿败血症（NS）是新生儿死亡的重要原因，常伴有急性肺损伤（ALI）。铁死亡在传染病中起作用，但其在NS相关ALI中的调控机制尚不清楚。本研究旨在探讨EMX2OS在促进ALI中铁死亡的机制。
通过临床样本检测NS患者外周血中EMX2OS的表达水平及其诊断价值。采用脂多糖（LPS）诱导的A549细胞建立ALI模型。通过qRT-PCR、CCK-8、检测试剂盒和双荧光素酶测定验证EMX2OS、miR-654-3p和AKT3之间的靶向关系，并评估细胞活力和铁死亡水平。
EMX2OS在NS中高表达，可作为潜在的诊断标志物。在LPS诱导的肺损伤模型中，EMX2OS的高表达降低了细胞活力，增强了铁死亡。沉默EMX2OS则产生相反的效果。EMX2OS通过miR-654-3p/AKT3轴调节细胞活力和铁死亡。
本研究首次揭示EMX2OS作为NS的诊断标志物，并通过miR-654-3p/AKT3轴促进铁死亡，从而加重肺损伤。EMX2OS调节铁死亡可能成为肺损伤的潜在治疗策略。
