Knockdown of NEAT1 mitigates ox-LDL-induced injury in human umbilical vein endothelial cells via miR-30c-5p/TCF7 axis

Abstract

Objective: Atherosclerosis is an inflammation-associated disease resulting in a huge health hazard. Abundance of researches showed that long non-coding RNAs (lncRNAs) played vital roles in atherosclerosis, but the molecular mechanism of nuclear-enriched abundant transcript (NEAT1) has not been fully elucidated yet.

Patients and methods: Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) for constructing the model of atherosclerosis. The detection of NEAT1, microRNA-30c-5p (miR-30c-5p), and transcription factor 7 (TCF7) expression was implemented by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Cell proliferation and apoptosis were measured by 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) and flow cytometry, respectively. The levels of apoptosis-associated proteins were examined through Western blot and the concentrations of inflammatory cytokines were determined by enzyme-linked immunosorbent assay (ELISA). The targeted relationship was analyzed by Dual-Luciferase reporter assay.

Results: NEAT1 was upregulated in serum of patients with atherosclerosis and HUVECs treated with ox-LDL. Knockdown of NEAT1 exerted the promotion of proliferation but suppression of apoptosis and inflammation in ox-LDL-treated HUVECs. Moreover, NEAT1 targeted miR-30c-5p and the overexpression of miR-30c-5p reversed the ox-LDL-induced effects in HUVECs. Furthermore, miR-30c-5p directly refrained the TCF7 level, and NEAT1 repression decreased the expression of TCF7 by upregulating miR-30c-5p. The knockdown of NEAT1 afforded the protective effect for HUVECs treated with ox-LDL through miR-30c-5p/TCF7 axis.

Conclusions: The knockdown of NEAT1 overtly motivated proliferation but alleviated the apoptosis and inflammation in ox-LDL-treated HUVECs by miR-30c-5p/TCF7 axis. NEAT1 accelerated the progression of atherosclerosis therapies, functioning as an indicative element.