Knockdown of long noncoding RNA MEG3 impairs VEGF-stimulated endothelial sprouting angiogenesis via modulating VEGFR2 expression in human umbilical vein endothelial cells

Abstract

Long noncoding RNAs is a novel class of RNA molecules, which is closely related to the occurrence and development of human disease. Recent studies have highlighted the importance of MEG3 in angiogenesis and the maintenance of normal function of vascular endothelial cells. However, whether MEG3 contributes to human endothelial cell angiogenesis as well as potential mechanisms are largely unknown. In this work, we found that the high expression level of MEG3 in primary HUVEC was controlled by DNA methylation, and its expression in HUVEC was regulated by HIF-1α under hypoxia condition. Meanwhile, we discovered that knockdown of MEG3 significantly suppressed VEGFR2 mRNA level, but had no influence on gene expression of VEGFR1, Notch1, DLL4 and Hes1. MEG3 reduction also suppressed VEGF-induced endothelial migration and angiogenesis. Furthermore, MEG3 knockdown reduced the tube formation and the spheroid sprouting of primary HUVEC under normoxic and hypoxic conditions. Altogether, MEG3 regulated by HIF-1α is required to maintain VEGFR2 expression in endothelial cells and plays a vital role for VEGFA-mediated endothelial angiogenesis.