miRNA‐34a promotes proliferation of human pulmonary artery smooth muscle cells by targeting PDGFRA

Abstract Objectives Pulmonary arterial hypertension ( PAH ) is a fast progressing vascular disease characterized by uncontrolled cell proliferation of pulmonary artery smooth muscle cells ( PASMC s). Some studies have suggested that PAH and cancers share an apoptosis‐resistant state, featuring excessive cell proliferation. The miR‐34 family consists of tumour‐suppressive mi RNA s, and its reduced expression has been reported in numerous cancers; however, its role in hypoxia‐induced PAH has not been previously studied. Materials and methods miR‐34 family expression was evaluated in a rat model with hypoxia and in cultured hypoxic PASMC s, using real‐time quantitative PCR ( RT ‐ qPCR ). Function of miR‐34 family was assessed by transfecting miR‐34 mimics and inhibitors. Dual luciferase reporter gene assays, RT ‐ qPCR and Western blotting were performed to validate target genes of miR‐34. Results Significant down‐regulation of miR‐34a in hypoxic lung tissue, pulmonary artery and PASMC s was identified and then effects of miR‐34a in modulating cell proliferation in human pulmonary artery smooth muscle cells ( hPASMC s) was investigated in vitro. Reduction of miR‐34a levels in hPASMC s caused increased proliferation and these effects were reversed by overexpression of miR‐34a. miR‐34a overexpression down‐regulated platelet‐derived growth factor receptor alpha ( PDGFRA ) expression, which is a key factor in PAH development. These results suggest that miR‐34a is a potential regulator of proliferation in PASMC s, and that it could be used as a novel treatment strategy in PAH.