文献类型：期刊文献

英文题名：hsa_circ_0000514/hsa_miR-3612/ACSL4 Axis Regulates Ferroptosis in Sepsis-Induced Acute Lung Injury

作者：Chen, Qiming[1,2];Dai, Lirong[3];Li, Bin[2];Zhu, Lei[2];Dou, Zhimin[2];Yue, Yinghua[2];Ai, Qingjuan[2];Liu, Jian[1,4]

第一作者：Chen, Qiming

通信作者：Liu, J[1];Liu, J[2]

机构：[1]Lanzhou Univ, Sch Clin Med 1, Lanzhou, Gansu, Peoples R China;[2]Lanzhou Univ, Hosp 1, Intens Care Unit, Lanzhou, Gansu, Peoples R China;[3]Gansu Univ Chinese Med, Sch Basic Med Sci, Lanzhou, Gansu, Peoples R China;[4]Gansu Prov Cent Hosp, Gansu Prov Matern & Child Care Hosp, Intens Care Unit, Lanzhou, Gansu, Peoples R China

第一机构：Lanzhou Univ, Sch Clin Med 1, Lanzhou, Gansu, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Sch Clin Med 1, Lanzhou, Gansu, Peoples R China;[2]corresponding author), Gansu Prov Cent Hosp, Gansu Prov Matern & Child Care Hosp, Intens Care Unit, Lanzhou, Gansu, Peoples R China.

年份：2026

卷号：2026

期号：1

外文期刊名：INTERNATIONAL JOURNAL OF CLINICAL PRACTICE

收录：;Scopus(收录号：2-s2.0-105044470061);WOS:【SCI-EXPANDED(收录号:WOS:001817605600001)】；

基金：This study was supported by the Gansu Provincial Natural Science Foundation (Grant no. 24JRRA1073), Wu Jieping Medical Foundation (Grant no. 320.6750.2022-02-8), and Hospital Fund of The First Hospital of Lanzhou University (ldyyyn2022-11).

语种：英文

外文关键词：ACSL4; ferroptosis; hsa-miR-3612; hsa_circ_0000514; sepsis-induced acute lung injury

摘要：Background Both ferroptotic cell death and circular RNA dysregulation have been implicated in sepsis-induced acute lung injury (sALI); accordingly, this study set out to delineate their interactive roles in sALI pathogenesis. Methods Differentially expressed circRNAs (GSE244903) and mRNAs (GSE10474) were screened by bioinformatics, and WGCNA was performed to identify sALI-associated co-expression modules. An LPS-treated BEAS-2B cell model was used to assess viability, ROS, Fe2+, and ferroptosis-related proteins (ACSL4, GPX4, and SLC7A11). The effects of si-hsa_circ_0000514, hsa-miR-3612 mimics, and combined overexpression were examined. Dual-luciferase assays and AGO2-RIP verified the interaction among hsa_circ_0000514, hsa-miR-3612, and ACSL4. An in vivo ALI model was also applied to evaluate the impact of AAV-mediated silencing of hsa_circ_0000514. Results A total of the top 16 circRNAs and 70 mRNAs with significant differential expression (|log(2)FC| > 1 and p < 0.05) were identified. WGCNA identified 1002 hub genes, and GPX4, ACSL4, and SLC7A11 all had AUC > 0.7. In cells, hsa_circ_0000514 was upregulated by LPS, while hsa-miR-3612 was downregulated. Silencing hsa_circ_0000514 or overexpressing hsa-miR-3612 reduced LPS-induced injury and ferroptosis, and hsa-miR-3612 partially reversed the role of hsa_circ_0000514. Additionally, hsa_circ_0000514 bound hsa-miR-3612 to regulate ACSL4. In vivo, hsa_circ_0000514 knockdown alleviated lung pathology, suppressed ACSL4, restored GPX4/SLC7A11, and reduced ROS and Fe2+. Conclusion hsa_circ_0000514 promotes ferroptosis in sALI through the hsa-miR-3612/ACSL4 axis. Silencing this circRNA protects against LPS-induced damage in vitro and in vivo, suggesting a potential therapeutic target for sALI.