RESUMO
Long noncoding RNAs (lncRNAs) have been validated to mediate the development of atherosclerosis (AS). In the present study, the molecular mechanisms and functions of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in the advancement of human aortic endothelial cells (HAECs) were investigated. The levels of lncRNANEAT1 and miR638 expression in clinical samples and cells were explored via quantitative reverse transcription polymerase chain reaction. Colony formation and CCK8 assays were performed to determine the proliferative capacity of cells, and the apoptotic capacity of cells was analyzed on the basis of apoptotic cell proportion and caspase3 activity. Then, the proportion of cells and correlations among phosphoglycerate kinase 1 (PGK1), NEAT1, and miR638 were determined through RNA immunoprecipitation and luciferase assays and bioinformatics analysis. Moreover, the expression levels of Ki67, proliferating cell nuclear antigen, PGK1, Bax, Bcl2, (p)mTOR, (p)AKT, and ßcatenin were analyzed via western blot analysis. In the serum of patients with AS and HAECs induced by oxidized lowdensity lipoprotein (oxLDL), the expression level of miR638 was decreased, whereas that of NEAT1 was increased. After oxLDL therapy, NEAT1 knockdown suppressed HAEC proliferation and stimulated HAEC apoptosis, which could be reversed by the miR638 inhibitor. NEAT1 inhibited miR638 expression through direct mutual action. The following mechanical investigations revealed that PGK1 was a miR638 target, whose expression was increased by NEAT1, a competing endogenous RNA of miR638. Additionally, the miR638 inhibitor contributed to proliferation and suppressed apoptosis through the activation of the AKT/mTOR signaling pathway in oxLDLinduced HAECs. NEAT1 adjusted the AKT/mTOR signaling pathway via miR638 in oxLDLinduced HAECs to accelerate their proliferation and impede their apoptosis. This result revealed that NEAT1 may be valuable in the treatment of AS.
