MicroRNA miR-627-5p restrains pulmonary artery smooth muscle cell dysfunction by targeting MAP2 K4 and PI3K/AKT signaling.

Abstract

BackgroundChronic obstructive pulmonary disease (COPD) is characterized by pulmonary vascular remodeling, which can be caused by abnormal proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). Several microRNAs were demonstrated to regulate the PASMC dysfunction. Our study intends to evaluate whether miR-627-5p affects cigarette smoke extract (CSE)-induced aberrant biological behaviors of PASMCs.MethodsPASMCs was treated with CSE to create the in vitro cellular model of COPD. The viability and LDH release of PASMCs was detected by CCK-8 assay and LDH release assay. MiR-627-5p and MAP 2 K4 expression in CSE (2%)-treated PASMCs was detected by qRT-PCR. PASMC proliferation was observed under a microscope, and PASMC migration was assessed by Transwell migration assays. The binding of miR-627-5p on MAP 2 K4 was verified by dual-luciferase reporter assay. Protein levels of MAP2K4 and the PI3K/AKT signaling markers were examined by western blotting.ResultsThe viability of PASMCs treated with 2% CSE reached a peak. CSE dose-dependently downregulated miR-627-5p expression in PASMCs. MiR-627-5p overexpression attenuated the CSE-induced abnormal proliferation and migration of PASMCs. However, MAP2K4 overexpression antagonized the effects of miR-627-5p on PASMC dysfunction. Importantly, miR-627-5p inhibited CSE-stimulated activation of the PI3K/AKT pathway via downregulating MAP2K4.ConclusionMiR-627-5p improves CSE-induced abnormal proliferation and migration of PASMCs by inhibiting MAP2K4 expression and the PI3K/AKT pathway.