Suppression of circXPO1 attenuates cigarette smoke-induced inflammation and cellular senescence of alveolar epithelial cells in chronic obstructive pulmonary disease.

Smoking is an essential facet of the pathogenesis of chronic obstructive pulmonary disease (COPD), which is typically characterized by inflammation and cellular senescence of alveolar epithelial cells. In this study, we investigated the function and fundamental mechanism of a novel circular RNA XPO1 (circXPO1) in cigarette smoke (CS)-induced inflammation and cellular senescence of alveolar epithelial cells. We found that circXPO1 was overexpressed in the lungs of CS-exposed mice and the CS extract (CSE)-treated alveolar epithelial cell line MLE12. Suppression of circXPO1 inhibited CSE-induced inflammatory cytokine production and cellular senescence. In vivo assays also demonstrated that circXPO1 knockdown attenuates CS-induced inflammation and senescence in the mouse lungs. Mechanistically, circXPO1 can directly bind to miR-23b-3p, preventing miR-23b-3p from binding to its target TGF-β-activated kinase 1/MAP3K7 binding protein 3 (TAB3)mRNA. In addition, under CSE conditions, miR-23b-3p overexpression recapitulated the prophylactic effects of circXPO1 knockdown. Inhibition of miR-23b-3p attenuated the function of circXPO1 knockdown in CSE-treated MLE12 cells. These results reveal that circXPO1 plays a role in the pathogenesis of COPD by modulating TAB3 through sponging miR-23b-3p.