LINC1810064F22Rik sequesters miR-206-5p away from HDAC4 to exacerbate allergic airway inflammation and airway remodeling in an ovalbumin mouse model of asthma
Huang, B.; Liu, M.; Le, G.
International Immunopharmacology 119: 110097
ISSN/ISBN: 1878-1705 PMID: 37068338 Accession: 090140626
Allergic inflammation and airway remodeling frequently occur in asthma. This study clarifies a novel LINC1810064F22Rik-mediated ceRNA mechanism involved in asthma-induced allergic inflammation and airway remodeling based on bioinformatics analysis and in vivo and in vitro experiments. The differentially expressed lncRNAs and downstream effectors were predicted in silico. The targeting relationship among LINC1810064F22Rik, miR-206-5p, and HDAC4 was predicted by bioinformatics analysis, which was further validated by dual luciferase reporter gene assay. The asthma-like airway inflammation was induced in mice using ovalbumin (OVA) sensitization/challenge with immune adjuvant Al(OH)3, while alveolar epithelial cells (AECs) were exposed to IL-33 to mimic in vitro inflammatory environment. LINC1810064F22Rik and HDAC4 were highly expressed, while miR-206-5p was poorly expressed in the tracheal tissues of OVA mice and the IL-33-treated AECs. The OVA mice and IL-33-treated AECs were subjected to gain- or loss-of-function experiments to detect the interaction of LINC1810064F22Rik/miR-206-5p/HDAC4 axis and their effects on allergic inflammation and airway remodeling. LINC1810064F22Rik competitively bound to miR-206-5p, and miR-206-5p targeted and inhibited HDAC4. The in vivo animal experiments indicated that LINC1810064F22Rik promoted asthma-induced allergic inflammation and airway remodeling by sequestering miR-206-5p away from HDAC4. The evidence provided by our study highlighted the involvement of the LINC1810064F22Rik/miR-206-5p/HDAC4 axis in facilitating allergic airway inflammation and airway remodeling in OVA mice.