Open Access

ARTICLE

Upregulation of microRNA-451a improves endothelial cell function in atherosclerosis by direct targeting of macrophage migration inhibitory factor

HONGXIA HU^*, PING GUO, QIAN ZHAO, HAORAN LI, HUALEI LIU, CAIHONG MA

Department of Laboratory Medicine, Henan Provincial Hospital, Zhengzhou, 450000, China

* Address correspondence to: Hongxia Hu,

BIOCELL 2021, 45(4), 995-1004. https://doi.org/10.32604/biocell.2021.012851

Received 15 July 2020; Accepted 21 December 2020; Issue published 22 April 2021

Abstract

This study aims to detect the expression of selected circulating microRNAs (miRNA), including miRNA-451a, miRNA-486-5p and miR-10b-5p, and their prospective roles as biomarkers in patients with atherosclerosis. For this purpose, levels of miRNAs were detected by real-time quantitative polymerase chain reaction (RT-qPCR) in case (N = 30) and healthy control (N = 30) groups. Receiver operating characteristic (ROC) curve analysis was carried out to evaluate the diagnostic ability of miRNAs. The correlations of miR-451a with lipid parameters were evaluated using Pearson’s correlation coefficients. HUVEC tested by ox-LDL was used as a cellular model of atherosclerosis. Cell viability and apoptosis were detected by methyl thiazolyl tetrazolium (MTT) and flow cytometry (FC) assays. Luciferase assay was used to determine the miRNA binding site on target genes. The results showed that miRNA-451a expression level was significantly lower in patients than controls. ROC curve analysis showed that the areas under the curve (AUC) of plasma miRNA-451a was 0.90. The miRNA-451a expression level exhibited significant negative correlations with cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL). Besides, miRNA-451a specifically binds to the 3’UTR of macrophage migration inhibitory factor (MIF) and mediated the cell proliferation and apoptosis of HUVECs exposed to ox-LDL. Furthermore, overexpression of miRNA-451a promoted the proliferation and alleviated apoptosis of HUVECs exposed to ox-LDL, while this result was attenuated by macrophage migration inhibitory factor (MIF) overexpression. Therefore, miRNA-451a could be considered as a potential biomarker for atherosclerosis and miRNA- 451a might contribute to regulating atherosclerosis through targeting MIF.

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Keywords

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