MiR-4458 Regulates Autophagy and Apoptosis By Targeting P53 In Chronic Obstructive Pulmonary Disease.

Abstract Background: Chronic obstructive pulmonary disease (COPD) is a progressive chronic airway disease of which tobacco smoking is a main risk factor. Numerous studies have revealed that microRNAs participate in the pathogenesis of COPD by regulating cell autophagy and apoptosis. The goal of this study was to elucidate the potential mechanism of miR-4458 in COPD. Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to measure the levels of miR-4458 in cigarette smoke extract (CSE)-exposed human bronchial epithelial cells (HBECs) and peripheral blood mononuclear cells (PBMCs) of patients. The effects of miR-4458 on autophagy, cell viability and apoptosis in the CSE-exposed HBECs were assessed by western blot (WB), Cell Counting Kit-8 (CCK-8) assay and flow cytometric analysis. Targetscan and miRDB databases were used to predict the downstream targets of miR-4458.Luciferase reporter assay and rescue experiments were employed to ensure the target gene. Results: MiR-4458 was downregulated in CSE-exposed HBECs and PBMCs of COPD patients. The overexpression of miR-4458 attenuated autophagy and apoptosis in CSE-exposed HBECs, while the downregulation of miR-4458 led to opposite results. Bioinformatics analysis predicted that P53 was a target gene of miR-4458, and luciferase reporter assay further verified this prediction. Rescue experiments showed that miR-4458 regulated cell autophagy and apoptosis via the P53-mediated AKT–mTOR signaling pathway.Conclusions: This study reveals that miR-4458 plays a protective role in CSE-exposed HBECs. MiR-4458 is a promising therapeutic target for COPD treatment.