Severe acute lung injury (ALI) cause significant morbidity and mortality worldwide. MicroRNAs (miRNAs) are possible biomarkers and therapeutic targets for ALI. We aimed to explore the role of miR-762, a known oncogenic factor, in the pathogenesis of ALI. Levels of miR-762 in lung tissues of LPS-treated ALI mice and blood cells of patients with lung injury were measured. Injury of human lung epithelial cell line A549 was induced by LPS stimulation. A downstream target of miR-762, NFIX, was predicted using online tools. Their interactions were validated by luciferase reporter assay. Effects of targeted regulation of the miR-762/NFIX axis on cell proliferation, apoptosis, and inflammatory responses were tested in vitro in A549 cells in vivo with an ALI mouse model. We found that upregulation of miR-762 expression and downregulation of NFIX expression were associated with lung injury. Either miR-762 inhibition or NFIX overexpression in A549 lung cells significantly attenuated LPS-mediated impairment of cell proliferation and viability. Notably, increasing expressions of miR-762 inhibitor or NFIX in vivo via airway lentivirus infection alleviated the LPS-induced ALI in mice. Further, targeted downregulation of miR-762 expression or upregulation of NFIX expression in A549 cells markedly down-regulates NF-κB/IRF3 activation, and substantially reduces the production of inflammatory factors, including TNF-α, IL-6, and IL-8. This study reveals a novel role for the miR-762/NFIX pathway in ALI pathogenesis and sheds new light on targeting this pathway for diagnosis, prevention, and therapy.

严重的急性肺损伤 (ALI) 在世界范围内导致显着的发病率和死亡率。MicroRNAs (miRNAs) 是 ALI 可能的生物标志物和治疗靶点。我们旨在探索已知致癌因子 miR-762 在 ALI 发病机制中的作用。测量 LPS 处理的 ALI 小鼠肺组织和肺损伤患者血细胞中 miR-762 的水平。LPS刺激诱导人肺上皮细胞系A549的损伤。使用在线工具预测了 miR-762 的下游靶标 NFIX。它们的相互作用通过荧光素酶报告基因测定得到验证。在体内A549 细胞中体外测试了 miR-762/NFIX 轴的靶向调节对细胞增殖、凋亡和炎症反应的影响使用 ALI 鼠标模型。我们发现 miR-762 表达的上调和 NFIX 表达的下调与肺损伤有关。A549 肺细胞中 miR-762 的抑制或 NFIX 过表达显着减弱了 LPS 介导的细胞增殖和活力损伤。值得注意的是，增加体内miR-762 抑制剂或 NFIX的表达通过气道慢病毒感染减轻了 LPS 诱导的小鼠 ALI。此外，靶向下调 A549 细胞中 miR-762 表达或上调 NFIX 表达显着下调 NF-κB/IRF3 活化，并显着减少炎症因子（包括 TNF-α、IL-6 和 IL-8）的产生. 这项研究揭示了 miR-762/NFIX 通路在 ALI 发病机制中的新作用，并为靶向该通路进行诊断、预防和治疗提供了新的思路。