Clinical Significance of DPP10-AS1 and Its Potential Mechanism in Chronic Obstructive Pulmonary Disease through miR-34c-5p.

Abstract

Chronic obstructive pulmonary disease (COPD) is a leading cause of global mortality, characterized by persistent airflow limitation and chronic inflammation. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play regulatory roles in COPD pathogenesis, but the function of DPP10-AS1 remains unclear. This study aimed to investigate the expression pattern, diagnostic value and functional mechanism of DPP10-AS1 in COPD, particularly its role in cigarette smoke-induced airway epithelial injury in 16HBE cells. Bioinformatic analysis of the GSE201465 dataset identified DPP10-AS1 as significantly up-regulated in COPD. Clinical validation was performed in 80 COPD patients and 80 controls. In vitro, 16HBE cells were treated with cigarette smoke extract (CSE) following DPP10-AS1 knockdown/over-expression. The interaction between DPP10-AS1 and miR-34c-5p was verified through RNA pull-down and dual-luciferase reporter assays. Functional rescue experiments with miR-34c-5p inhibitor in DPP10-AS1-silenced cells under CSE exposure were constructed. DPP10-AS1 expression was markedly elevated in COPD patients, showing a significant correlation with impaired lung function (FEV1/FVC: r = -0.743). It presented a diagnostic potential (AUC = 0.806). CSE exposure up-regulated DPP10-AS1 in 16HBE cells, which exacerbated inflammation (IL-6, IL-8 and COX-2) and fibrosis (α-SMA, Col1A1 and TGF-β1). Our research results indicated that DPP10-AS1 acts as a "molecular sponge" for miR-34c-5p. This mecha-nism may be of great significance for its role in COPD. We concluded that DPP10-AS1 promotes CSE-induced airway inflammation and remodelling through miR-34c-5p in 16HBE cells, suggesting its potential involvement in COPD progression. These findings combined with clinical analysis position DPP10-AS1 as a candidate diagnostic biomarker and therapeutic target.