Long non‑coding RNA HOTAIR knockdown alleviates lipopolysaccharide‑induced acute respiratory distress syndrome and the associated inflammatory response by modulating the microRNA‑30a‑5p/PDE7A axis

Acute respiratory distress syndrome (ARDS) is a severe pulmonary disease, which can be modulated by certain long non-coding (lnc)RNAs. The present study aimed to investigate the regulatory mechanism of lncRNA HOTAIR in ARDS and the inflammatory response induced by lipopolysaccharide (LPS). The mRNA expression levels of HOTAIR, microRNA (miR)-30a-5p and PDE7A were determined using reverse transcription-quantitative PCR, while a MTT assay was used to assess the viability of the MLE-12 cells and ELISA was used to determine the concentration of different inflammatory factors [tumor necrosis factor (TNF)-α, IL-1β and IL-6]. The interactions between miR-30a-5p and HOTAIR/PDE7A were predicted using TargetScan and StarBase databases and verified using a dual-luciferase reporter assay. The protein expression levels of PDE7A were determined using western blot analysis. Mouse models of LPS-induced ARDS were established to investigate the suppressive effect of HOTAIR knockdown on ARDS in vivo. lncRNA HOTAIR was increased in LPS-treated MLE-12 cells and in a ARDS mouse model. HOTAIR knockdown decreased the concentration of TNF-α, IL-1β and IL-6, and increased cell viability in vitro. miR-30a-5p upregulation decreased TNF-α, IL-1β and IL-6 concentrations, and increased cell viability in vitro. HOTAIR targeted miR-30a-5p and miR-30a-5p targeted PDE7A. miR-30a-5p downregulation and PDE7A upregulation reversed the suppressive effect of HOTAIR knockdown on the concentrations of TNF-α, IL-1β and IL-6, and the positive effect of HOTAIR knockdown on cell viability in vitro. HOTAIR knockdown also attenuated ARDS and the inflammatory response induced by LPS in vivo. The suppression of HOTAIR alleviated ARDS and the inflammatory response induced by LPS by modulating the miR-30a-5p/PDE7A axis. These results provide a potential therapeutic strategy for ARDS.

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