LncRNA ZFAS1 promotes ox-LDL induced EndMT through miR-150-5p/Notch3 signaling axis

Abstract

EndMT is an active contributor to atherosclerosis pathology, and lncRNAs is widely involved in the occurrence and development of atherosclerosis. The purpose of this study was to investigate the regulatory mechanisms of ZFAS1 in EndMT of atherosclerosis. Here, the ApoE−/− mice were feed with high-fat diet to establish the atherosclerosis model, and HUVECs was stimulated with ox-LDL to induce EndMT. RT-PCR and western blot were used to detect the mRNA and protein expression, respectively. The expression of EndMT markers were detected by immune-fluorescence. The relationships among ZFAS1, miR-150-5p and Notch3 were evaluated by luciferase reporter assay. The role of ZFAS1 in EndMT and its dependence on miR-150-5p/Notch3 axis was further detected by knocking down or over-expressing ZFAS1. We found that ZFAS1 and Notch3 were upregulated while miR-150-5p was downregulated in atherosclerosis mice and ox-LDL-treated HUVECs. The expression of CD31 and vWF were significant decreased, while the α-SMA and vimentin were significant increased in ox-LDL-treated HUVECs, and overexpression of ZFAS1 enhanced the effect of ox-LDL on HUVECs. Further, ZFAS1 functions as a ceRNA to increase Notch3 expression through sponging miR-150-5p, and miR-150-5p mimic or si-Notch3 could reverse LV-ZFAS1-mediated EndMT. In summary, lncRNA ZFAS1 promotes ox-LDL induced HUVECs EndMT through regulating miR-150-5p/Notch3 axis.