Long noncoding RNA GAS5 attenuates cigarette smoke-induced airway remodeling by regulating miR-217-5p/PTEN axis.

Abstract

Airway remodeling is a remarkable pathological characteristic of chronic obstructive pulmonary disease (COPD), and long noncoding RNAs have been demonstrated to participate in COPD development and pathogenesis. Here, we investigate the role of long noncoding RNA GAS5 in cigarette smoke (CS)-induced airway remodeling. GAS5 expression is significantly lower in lung tissues of CS-exposed mice than in tissues of control mice without exposure to CS. Forced GAS5 overexpression suppresses CS-induced airway inflammation and remodeling. GAS5 overexpression also inhibits CS extract-induced inflammatory-cytokine expression and fibroblast activation in vitro. Regarding the mechanism, GAS5 acts as a sponge of miR-217-5p, thereby increasing PTEN expression. MiR-217-5p overexpression and PTEN knockdown separately reverse the inhibitory effects of GAS5 overexpression on the inflammatory-cytokine expression and fibroblast activation. Collectively, these results suggest that GAS5 can suppress airway inflammation and fibroblast activation by regulating miR-217-5p/PTEN axis, which may help develop novel therapeutic strategies against COPD.