A miRNA-21-Mediated PTEN/Akt/NF-κB Axis Promotes Chronic Obstructive Pulmonary Disease Pathogenesis

Xiaoyan Sai,* Chu Qin,* Zixiao Zhang,* Haoda Yu, Tao Bian Department of Respiratory Medicine, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, 214000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haoda Yu, Department of Respiratory Medicine, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, 214000, People’s Republic of China, Email yhd9988@sina.com Tao Bian, Department of Respiratory Medicine, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, 214000, People’s Republic of China, Email biantaophd@126.comBackground: This study sought to explore the underlying mechanism of miR-21 mediated apoptosis and inflammation in chronic obstructive pulmonary disease (COPD) induced by cigarette smoke (CS).Methods: We detected levels and PTEN/Akt/NF-κB axis protein levels in peripheral lung tissues of COPD patients and CS-exposed mice and HBE cells. Western blotting assay was used to determine the expression of cleaved caspase-3. IL-6 and IL-8 protein was detected in cell supernatant from cells by ELISA. HBE cells were transfected with a miR-21 inhibitor, and co-culture with A549.Results: Increased miR-21 expression, reduced PTEN expression and following activation of Akt in in peripheral lung tissues of COPD patients and CS-exposed mice and HBE cells. Inhibition of miR-21 showed enhanced PTEN levels and reduced the expression of phosphorylated form of Akt and NF-κB. Decreased expression of cleaved caspase-3, IL-6 and IL-8 in A549 cells co cultured with HBE cells transfected with miR-21 inhibitor compared with transfected with miR-21 control inhibitor.Conclusion: MiR-21 contributes to COPD pathogenesis by modulating apoptosis and inflammation through the PTEN/Akt/NF-κB pathway. Targeting miR-21 may increase PTEN expression and inhibit Akt/NF-κB pathway, offering potential diagnostic and therapeutic value in COPD management.Keywords: COPD, miR-21, PTEN/Akt/NF-κB axis, apoptosis, inflammation