Background: MicroRNAs (miRNAs) are linked to asthma progression. In this study, we aimed to decipher the functional role of miR-140 and delineate its link to the mechanism behind the progression of asthma.

Methods: BALB/c mice were divided into four groups, designated as control, asthma, Agomir negative control (NC), and Agomir group. In vitro model of asthma using transforming growth factor-beta 1 (TGF-β1)-treated 16HBE cells, and cells transfected with glycogen synthase kinase 3β (GSK3β) overexpression plasmid or Agomir miR-140. Real-time quantitative polymerase chain reaction (RT-qPCR) was to test miR-140 abundance. Hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) of lung tissues for examining their histopathological changes. Enzyme-linked immunosorbent assay (ELISA) and in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were to test inflammatory factors levels and cell apoptosis, respectively. B-cell lymphoma 2 (Bcl-2), GSK3β, cleaved caspase-3 and Bcl-2 associated X protein (BAX) protein levels were evaluated using Western blotting. GSK3β expression was also detected using immunohistochemistry (IHC). RNA immunoprecipitation (RIP) and dual-luciferase reporter assay were to verify the correlation between GSK3β and miR-140.

Results: Both the asthma mice and TGF-β1-treated 16HBE cells exhibited decreased miR-140 level and increased protein expression of GSK3β (p < 0.001). Compared with the asthma mice, overexpression of miR-140 significantly relieved airway inflammation and reduced cell apoptosis (p < 0.001). Targeted relationship existed between GSK3β and miR-140, and the overexpression of miR-140 dramatically repressed the level of GSK3β in asthma group and TGF-β1-treated 16HBE cells (p < 0.001). Nevertheless, the suppressive impacts of miR-140 overexpression were hindered by GSK3β upregulation in TGF-β1-treated 16HBE cells (p < 0.01 or p < 0.001).

Conclusions: miR-140 mitigates airway inflammation and represses apoptosis in asthma by targeting and regulating GSK3β.