Pulmonary arterial hypertension (PAH) is featured by the increase in pulmonary vascular resistance and pulmonary arterial pressure. Despite that abnormal proliferation and phenotypic changes in human pulmonary artery smooth muscle cells (HPASMCs) contributing to the pathophysiology of PAH, the underlying molecular mechanisms remain unclear. In the present study, we detected the expression of miR-629 in hypoxia-treated HPASMCs and explored the mechanistic role of miR-629 in regulating HPASMC proliferation, migration and apoptosis. Hypoxia time-dependently induced up-regulation of miR-629 and promoted cell viability and proliferation in HPASMCs. Treatment with miR-629 mimics promoted HPASMCs proliferation and migration, but inhibited cell apoptosis; while knockdown of miR-629 suppressed the cell proliferation and migration but promoted cell apoptosis in HPASMCs. The bioinformatics prediction revealed FOXO3 and PERP as downstream targets of miR-629, and miR-629 negatively regulated the expression of FOXO3 and PERP via targeting the 3' untranslated regions. Enforced expression of FOXO3 or PERP attenuated the miR-629 overexpression or hypoxia-induced enhanced effects on HPASMC proliferation and proliferation, and the suppressive effects on HPASMC apoptosis. Furthermore, the expression of miR-629 was up-regulated, and the expression of FOXO3 and PERP mRNA was down-regulated in the plasma from PAH patients when compared to healthy controls. In conclusion, the present study provided evidence regarding the novel role of miR-629 in regulating cell proliferation, migration and apoptosis of HPASMCs during hypoxia.
Keywords: FOXO3; PAH; PERP; PHASMCs; hypoxia; miR-629.
© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.