Silencing of long non-coding RNA KCNQ1OT1 alleviates LPS-induced lung injury by regulating the miR-370-3p/FOXM1 axis in childhood pneumonia

• Published in: BMC pulmonary medicine Vol. 21; no. 1; pp. 1 - 247
• Main Authors: Wang, Ping, Zhang, Haitao, Zhao, Weiqing, Dai, Nini
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 23.07.2021; BioMed Central; BMC
• Subjects: Age; Apoptosis; Binding sites; Cell viability; Children; Development and progression; Diploids; Embryo fibroblasts; Embryos; Fibroblasts; Forkhead box protein M1; Gene silencing; Genetic aspects; Health aspects; Immunoprecipitation; Inflammation; KCNQ1 overlapping transcript 1; KCNQ1OT1 protein; Lipopolysaccharides; Long non-coding RNA; Lungs; miR-370-3p; Non-coding RNA; Pathogens; Pediatric research; Physiological aspects; Pneumonia; Pneumonia in children; Potassium channels (voltage-gated); Proteins; Pulmonology; RNA; RNA-binding protein; RNA-mediated interference; Standard deviation; China; United States > US
• ISSN: 1471-2466; 1471-2466
• DOI: 10.1186/s12890-021-01609-0

Abstract Purpose Long non-coding RNAs (lncRNAs) play important roles in the development of pneumonia. We aimed to explore the role of the lncRNA KCNQ1OT1 in pneumonia and its underlying mechanisms. Methods The expression of KCNQ1OT1, FOXM1, and miR-370-3p was detected in the serum of 24 children with pneumonia and in 24 healthy controls. Normal human embryonic lung-derived diploid fibroblasts (WI-38 cells) were stimulated with LPS (10 μg/mL) to simulate the cellular model of pneumonia, and cell viability, apoptosis, and inflammation were analysed. Dual luciferase reporter and/or RNA binding protein immunoprecipitation assays were performed to test the relationship between miR-370-3p and KCNQ1OT1/FOXM1. Mice were intratracheally administered LPS (5 mg/kg) to induce an in vivo model of pneumonia, and pathological injury and inflammation were analysed. Results The expression of KCNQ1OT1 and FOXM1 was up-regulated, and miR-370-3p was down-regulated in the serum of children with pneumonia, LPS-treated WI-38 cells, and in lung tissues of LPS-treated mice. Silencing of KCNQ1OT1 or overexpression of miR-370-3p suppressed cell apoptosis and inflammation and facilitated cell viability in LPS-treated WI-38 cells. KCNQ1OT1 directly targets miR-370-3p and negatively regulates its expression. FOXM1 was targeted by miR-370-3p and negatively modulated by miR-370-3p. In addition, silencing of KCNQ1OT1 mitigated LPS-induced lung injury and inflammation in mice. The protective effects of KCNQ1OT1 silencing in LPS-treated WI-38 cells and mice were reversed by silencing of miR-370-3p or overexpression of FOXM1. Conclusion Silencing of KCNQ1OT1 alleviates LPS-induced lung injury by regulating the miR-370-3p/FOXM1 axis in pneumonia.