LncRNA XIST, as a ceRNA of miR-204, aggravates lipopolysaccharide-induced acute respiratory distress syndrome in mice by upregulating IRF2

Shuguang Wang; Feng Cao; Xingsheng Gu; Jianan Chen; Ranxing Xu; Yangneng Huang; Lina Ying

LncRNA XIST, as a ceRNA of miR-204, aggravates lipopolysaccharide-induced acute respiratory distress syndrome in mice by upregulating IRF2

Int J Clin Exp Pathol. 2019 Jul 1;12(7):2425-2434. eCollection 2019.

Authors

Shuguang Wang¹, Feng Cao², Xingsheng Gu¹, Jianan Chen¹, Ranxing Xu³, Yangneng Huang², Lina Ying³

Affiliations

¹ Department of Emergency Intensive Care Unit, Ningbo No. 6 Hospital Ningbo 315040, China.
² Department of Emergency, Ningbo No. 6 Hospital Ningbo 315040, China.
³ Department of Clinical Laboratory, Ningbo No. 6 Hospital Ningbo 315040, China.

PMID: 31934069
PMCID: PMC6949564

Abstract

Background: Acute respiratory distress syndrome (ARDS) is a common clinical syndrome with high a mortality rate, which is associated with diffuse alveolar injury and capillary endothelial damage. In recent years, numerous studies have been performed to explore the roles of long non-coding RNAs (lncRNAs) in various diseases in which lncRNA serves as a microRNA (miRNA) sponge to regulate targeted gene expression. However, whether lncRNAs participate in ARDS progression remains unclear.

Materials/methods: The dual-luciferase reporter assay was employed to identify the interaction between lncRNA XIST and miR-204, as well as the correlation between miR-204 and interferon regulatory factor 2 (IRF2). Then, PaO₂/FiO₂ was determined in lipopolysaccharide (LPS)-induced ARDS. In addition, the concentrations of cytokines, including IFN-γ, IL-6, IL-17, TNF-α, IL-1β, and IL-6R were analyzed by ELISA. lncRNA XIST, miR-204, and IRF2 levels were determined by qRT-PCR assay, and the IRF2 expression was evaluated by western blot. Furthermore, levels of inflammation and conditions of alveoli were evaluated by hematoxylin (H&E)-staining in LPS-induced ARDS.

Results: Our findings indicated that lncRNA XIST served as a sponge for miR-204. miR-204 directly regulated IRF2, andlncRNA XIST upregulated IRF2 expression by targeting miR-204. LncRNA XIST and miR-204 inhibitors significantly decreased the PaO₂/FiO₂ ratio, whereas miR-204 and silencing of IRF2 significantly increased the PaO₂/FiO₂ ratio in LPS-induced ARDS. In addition, lncRNA XIST and miR-204 inhibitors significantly increased levels of IFN-γ, IL-6, IL-17, TNF-α, IL-1β, and IL-6R, whereas miR-204 and silencing of IRF2 dramatically decreased related cytokines in LPS-induced ARDS. Furthermore, we demonstrated that lncRNA XIST and miR-204 inhibitors aggravated inflammatory cell infiltration, alveolitis, and the degree of fibrosis, whereas miR-204 and silencing of IRF2 alleviated inflammation and conditions of the alveoli.

Conclusion: In this study, we verified that lncRNA XIST serves as a sponge for miR-204 to aggravate LPS-induced ARDS in mice by upregulating IRF2.

Keywords: Acute respiratory distress syndrome; interferon regulatory factor 2; lncRNA XIST; microRNA-204.