NEAT1 knockdown suppresses endothelial cell proliferation and induces apoptosis by regulating miR‑638/AKT/mTOR signaling in atherosclerosis

Abstract

Long non-coding 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 lncRNA-NEAT1 and miR-638 expression in clinical samples and cells were explored via quantitative reverse transcription polymerase chain reaction. Colony formation and CCK-8 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 caspase-3 activity. Then, the proportion of cells and correlations among phosphoglycerate kinase 1 (PGK1), NEAT1, and miR-638 were determined through RNA immunoprecipitation and luciferase assays and bioinformatics analysis. Moreover, the expression levels of Ki-67, proliferating cell nuclear antigen, PGK1, Bax, Bcl-2, (p)-mTOR, (p)-AKT, and β-catenin were analyzed via western blot analysis. In the serum of patients with AS and HAECs induced by oxidized low-density lipoprotein (ox-LDL), the expression level of miR-638 was decreased, whereas that of NEAT1 was increased. After ox-LDL therapy, NEAT1 knockdown suppressed HAEC proliferation and stimulated HAEC apoptosis, which could be reversed by the miR-638 inhibitor. NEAT1 inhibited miR-638 expression through direct mutual action. The following mechanical investigations revealed that PGK1 was a miR-638 target, whose expression was increased by NEAT1, a competing endogenous RNA of miR-638. Additionally, the miR-638 inhibitor contributed to proliferation and suppressed apoptosis through the activation of the AKT/mTOR signaling pathway in ox-LDL-induced HAECs. NEAT1 adjusted the AKT/mTOR signaling pathway via miR-638 in ox-LDL-induced HAECs to accelerate their proliferation and impede their apoptosis. This result revealed that NEAT1 may be valuable in the treatment of AS.

Adenosine-to-inosine Alu RNA editing controls the stability of the pro-inflammatory long noncoding RNA NEAT1 in atherosclerotic cardiovascular disease

“…Endothelial cells (ECs) are key contributors to cardiovascular disease mainly due to their unique characteristic of “responding to injury” which is known as EC proinflammatory response and initiates a key chain of critical events for the disease development and progression [ 39 , 40 ]. Interestingly, NEAT1 lncRNA expression increases in response to exogenous administration of oxidized LDL [ 41 , 42 ] and high glucose [ 43 ] in ECs. We therefore tested whether NEAT1 lncRNA levels are altered during the EC proinflammatory response.…”

The Protective Effect of Liquiritin in Hypoxia/Reoxygenation-Induced Disruption on Blood Brain Barrier

“…ApoA1 is reported to regulate the expression of apolipoprotein in brain and reduce atherosclerosis ( Button et al, 2019 ; Contu et al, 2019 ). The increase of PGK1 can also reduce the formation of atherosclerosis ( Zhang et al, 2020 ). CEBPB is involved in the regulation of brain injury and inflammation ( Cortes-Canteli et al, 2008 ).…”

The Protective Effect of Quercetin on Endothelial Cells Injured by Hypoxia and Reoxygenation

“…HBA1 expression in endothelial cells has been shown to control vascular tone and function ( Sangwung et al, 2017 ). PGK1 is also thought to reduce atherogenesis ( Zhang et al, 2020 ). What’s more, VTN is considered critical for thrombus formation in the setting of vascular injury ( Bowley et al, 2017 ).…”