Upregulation of ARHGAP18 by miR-613 Inhibits Cigarette Smoke Extract-Induced Apoptosis and Epithelial-Mesenchymal Transition in Bronchial Epithelial Cells.

OBJECTIVE

Chronic Obstructive Pulmonary Disease (COPD) is a major chronic respiratory disease affecting human health worldwide. However, there is still a lack of effective drugs for treating COPD. This study is intended to explore the function and molecular mechanism of and miR-613 in COPD pathogenesis.

METHODS

We initially identified the marker gene closely related to epithelial dysfunction in COPD by integrating bioinformatic analyses. expression in CSE-induced bronchial epithelial cells (BEAS-2B) was detected by qRT-PCR. Besides, levels were modulated by lentivirus-mediated overexpression. Thereafter, cell variability, apoptosis, and migration were detected by CCK8, flow cytometry, and wound healing assay. IL-1β and TNF-α levels were examined by qRT-PCR. Epithelial-mesenchymal transition (EMT)-associated proteins were determined by Western blotting. The function of miR-613 in COPD was further detected. Functional rescue experiments were performed to determine the mechanism of in COPD.

RESULTS

Our study identified as the key gene associated with epithelial dysfunction in COPD. was downregulated in CSE-induced BEAS-2B cells. Overexpression of inhibited cell apoptosis of BEAS-2B cells and enhanced their proliferation and migration. Besides, overexpression reduced IL-1 β and TNF-α levels, enhanced E-cadherin expression, and suppressed Vimentin and N-cadherin expression. In contrast, miR-613 mimics exerted opposite effects. Furthermore, downregulation of , mediated by miR-613 inhibitor promoted cell apoptosis and EMT of CSE-induced BEAS-2B cells, suggesting a regulatory role of miR-613 in COPD pathogenesis.

CONCLUSION

These findings highlight miR-613/ axis as a critical regulator of epithelial dysfunction in COPD, offering a potential therapeutic target to counteract apoptosis, inflammation, and airway remodeling.