Decrease in LINC00963 attenuates the progression of pulmonary arterial hypertension via microRNA-328-3p/profilin 1 axis

Background Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary disease characterized by vascular hyperplasia and remodeling. Long noncoding RNA LINC00963 can regulate cell proliferation and metastasis in nonsmall cell lung cancer. However, the function of LINC00963 on PAH progression is rarely reported. Methods Quantitative real-time PCR was used to determine the expression levels of LINC00963, microRNA (miRNA)-328-3p, and profilin 1 (PFN1), as well as vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF-2), and hypoxia-inducible factor (HIF)-alpha. The protein level of PFN1 was measured by western blotting. The viability and migration of hypoxia-induced pulmonary arterial smooth muscle cells (PASMCs) were assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-h-tetrazolium bromide, and transwell assays, respectively. The target relationships between miR-328-3p and LINC00963/PFN1 were confirmed by dual-luciferase reporter assay. A PAH mouse model was conducted to explore the effects of hypoxia on cardiopulmonary functions. Results In hypoxia-induced PASMCs and PAH mouse model, high expression levels of LINC00963 and PFN1, and low expression of miR-328-3p, were determined. The viability, migration of hypoxia-induced PASMCs, the expression of VEGF, FGF-2, and HIF-alpha were significantly repressed by transfection of si-LINC00963 or miR-328-3p mimics. The inhibitory effects of LINC00963 silencing on cell viability, migration, and the levels of VEGF, FGF-2, and HIF-alpha were partly eliminated by miR-328-3p inhibitor or increasing the expression of PFN1. Hypoxia treatment increased the levels of RVSP, mPAP, and RV/(LV+S), as well as the thickness of pulmonary artery wall. Conclusions Silencing of LINC00963 ameliorates PAH via modulating miR-328-3p/PFN1.