Dysregulation of microRNA-214 and PTEN contributes to the pathogenesis of hypoxic pulmonary hypertension

Abstract

Hypoxia-induced pulmonary hypertension, which is characterized by vascular remodeling of blood vessels, is an important complication in COPD. In this study, we found that the expression of miR-214 was differentially expressed by screening 13 candidate miRNAs in pulmonary artery smooth muscle cells (PASMCs). Additionally, using luciferase assay in PASMCs, we found that phosphatase-and-tensin homolog (PTEN) was a target of miR-214. Furthermore, the expression of PTEN was found to be substantially downregulated in PASMCs from COPD patients with pulmonary hypertension (PH) compared with normal controls by using real-time polymerase chain reaction (PCR), immunohistochemistry, and Western blot. In addition, we transfected PASMCs with miR-214 mimics, using real-time PCR and Western blotting, to confirm the miRNA/mRNA relationship. Furthermore, the introduction of miR-214 significantly promoted the proliferation of PASMCs by suppressing apoptosis of the cells, which was mediated by the downregulation of PTEN. Exposure to hypoxia significantly increased the expression of miR-214 and decreased the expression of PTEN in PASMCs, and its proliferation was significantly promoted. Such effects could be significantly attenuated by the introduction of miR-214 inhibitors, which significantly downregulated miR-214 expression and upregulated the expression of PTEN. In conclusion, hypoxia-induced upregulation of miR-214 was found to promote PH development by targeting PTEN in PASMCs, and miR-214 could be a promising diagnostic tool and novel therapeutic target in the management of hypoxia-induced PH in COPD.