LncRNA GAS5 attenuates COPD pathogenesis by stabilizing p120 catenin to suppress NF-κB-driven inflammation

To investigate the role of lncRNA GAS5 in COPD and its underlying mechanism. COPD mouse model was conducted as an in vivo inflammatory response model. CSE was used to stimulate human airway epithelial cells (16HBE) and human normal lung epithelial cells (BEAS-2B) to establish an in vitro inflammatory response model. Recombinant adenoviruses containing GAS5 or GAS5 shRNA were used to overexpression or knockdown of GAS5. The expression of p120/NF-κB was detected by RT-PCR and Western Blot. The distribution of NF-κB p65 protein in cells was detected by western blot and immunofluorescence staining. The expression levels of IL-6, IL-8 and TNF-α in downstream NF-κB were detected by RT-PCR and ELISA. The expression of lncRNA GAS5 was downregulated in COPD in vivo and in vitro. We showed that overexpression of GAS5 alleviates inflammation and NF-κB activation in COPD in vivo and in vitro. Moreover, we demonstrated that GAS5 regulate NF-κB activation by bind with p120. Knocking down of p120 inhibits the protective effect of GAS5 on inflammation. LncRNA GAS5 can bind with p120, enhance p120 stability and inhibit the NF-κB pathway and production of inflammatory factors downstream of NF-κB, thus playing a protective role in the airway.