MEG3 Regulates CSE-Induced Apoptosis by Regulating miR-421/DFFB Signal Axis

Hui Bi,1 Gui Wang,2 Zhiying Li,1 Lin Zhou,1 Ming Zhang1 1Department of Respiratory Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 2Department of Intensive Care Unit, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of ChinaCorrespondence: Hui Bi, Department of Respiratory Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213000, People’s Republic of China, Email bihui3000@126.comIntroduction: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with irreversible and progressive obstruction of airflow. Currently, there are no clinically available treatments to prevent COPD progression. Apoptosis of human lung microvascular endothelial cells (HPMECs) and bronchial epithelial cells (HBECs) is often observed in COPD, but its pathogenesis has not been fully elucidated. LncRNA maternally expressed gene 3 (MEG3) is closely related to CSE-induced apoptosis, but the specific mechanism of MEG3 in COPD is still unknown.Methods: In the present study, cigarette smoke extract (CSE) is used to treat HPMECs and HBECs. Flow cytometry assay is used to detect the apoptosis of these cells. The expression of MEG3 in CSE-treated HPMECs and HBECs is detected by qRT-PCR. LncBase v.2 is used to predict miRNAs binding to MEG3, and miR-421 is found to bind to MEG3. Dual luciferase report analysis and RNA immunoprecipitation experiment jointly clarified the binding relationship between MEG3 and miR-421.Results: MiR-421 was downregulated in CSE-treated HPMECs/HBECs, and miR-421 overexpression mitigated CSE-induced apoptosis in these cells. Subsequently, DFFB was found to be directly targeted by miR-421. The overexpression of miR-421 dramatically reduced the expression level of DNA fragmentation factor subunit beta (DFFB). DFFB was found downregulated in CSE-treated HPMECs and HBECs. MEG3 contributed to the apoptosis of HPMECs and HBECs induced by CSE by regulating the miR-421/DFFB axis.Conclusion: This study presents a new perspective on the diagnosis and treatment of COPD caused by CSE.Keywords: COPD, CSE, MEG3, miR-421/DFFB axis, apoptosis