• Clinics · Jan 2024

    CircRBM33 competitively binds miR-15a-5p to mediate EZH1 expression to ameliorate sepsis-induced acute lung injury.

    • Jinquan Lin, Qiongying Wei, and Zhipeng Fang.
    • Department of Trauma Center and Emergency Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou City, Fujian Province, PR China; Department of Trauma Center and Emergency Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou City, Fujian Province, PR China. Electronic address: JinquanLinin@outlook.com.
    • Clinics (Sao Paulo). 2024 Jan 1; 80: 100550100550.

    BackgroundThe study was to investigate circRBM33 in septic acute lung injury (ALI).MethodsTreatment of Murine Lung Epithelial-12 cells (MLE-12) cells was performed using 10 ng/mL Lipopolysaccharide (LPS). circRBM33, miR-15a-5p, and Enhancer of zeste homolog 1 (EZH1) were ascertained through RT-qPCR or Western blot analysis. The viability of MLE-12 cells was measured using the MTT assay, and their rate of apoptosis was ascertained through flow cytometry. B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X (Bax) were determined using Western blot analysis. Oxidative stress levels were assessed with ELISA kits, and levels of malondialdehyde(MDA) content, Superoxide Dismutase (SOD) activity, and glutathione (GSH) were detected. Dual luciferase reporter gene and RIP assays verified the targeting link between miR-15a-5p and circRBM33 or EZH1. The role of circRBM33 in ALI in vivo was determined by performing cecum ligation-perforation (CLP) surgery. HE staining, W/D pulmonary edema, and histological damage scores were taken to assess the extent of lung tissue damage. ELISA was performed to determine proinflammatory factors in lung tissue and cells.ResultsCircRBM33 downregulation ameliorated ALI-induced edema, apoptotic, and inflammatory reactions in mouse lung tissues. In addition, apoptosis and inflammation mediated by LPS in MLE-12 cells were ameliorated by circRBM33 downregulation, whereas miR-15a-5p knockdown or EZH1 elevation eliminated the action of silencing circRBM33. circRBM33 mediated EZH1 expression by competitive adsorption of miR-15a-5p.ConclusionCircRBM33 improves ALI in septic mice by targeting the miR-15a-5p/EZH1 axis.Copyright © 2024. Published by Elsevier España, S.L.U.

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