LncRNA-CCAT1/miR-152-3p is involved in CSE-induced inflammation in HBE cells via regulating ERK signaling pathway

Emerging studies have noted that dysregulated long non-coding RNAs (lncRNAs) are implicated in the pathological processes of chronic obstructive pulmonary disease (COPD). LncRNA colon cancer-associated transcript 1 (CCAT1) plays well-defined roles in the inflammatory progression. The study aims to figure out the effect and regulatory mechanism of CCAT1 in the cigarette smoke induced inflammation in COPD. The results showed that CCAT1 was highly expressed in lung tissues of smokers with COPD compared with never-smokers without COPD. In human bronchial epithelial (HBE) cells, cigarette smoke extract (CSE) treatment led to an increase in CCAT1 expression in a dose-and time-dependent manner. Functional experiments showed that knockdown of CCAT1 ameliorated CSE-induced inflammation. Mechanistically, CCAT1 directly targeted miR-152-3p, and miR-152-3p overexpression reversed the pro-inflammatory effects of CCAT1 on HBE cells. Subsequently, miR-152-3p was found to regulate ERK signaling pathway. PD98059, an ERK specific inhibitor, reversed miR-152-3p knockdown mediated inflammation in HBE cells. In addition, CCAT1 acted as a sponge for miR-152-3p to positively regulate ERK signaling pathway. Overall, current findings suggest that CCAT1 promoted inflammation by activating ERK signal pathway via sponging miR-152-3p in CSE-treated HBE cells. These results may provide a novel therapeutic target for alleviating cigarette smoke mediated airway inflammation.

Automated summary

This study demonstrates that dysregulated long non-coding RNA (lncRNA) CCAT1 plays a significant role in cigarette smoke induced inflammation in chronic obstructive pulmonary disease (COPD). CCAT1 is highly expressed in the lung tissues of smokers with COPD compared to never-smokers without COPD. It directly targets miR-152-3p and positively regulates the ERK signaling pathway, leading to inflammation in human bronchial epithelial cells.