LncRNA SNHG1 alleviates hypoxia-reoxygenation-induced vascular endothelial cell injury as a competing endogenous RNA through the HIF-1α/VEGF signal pathway.

Abstract

Long noncoding ribonucleic acids (lncRNAs) are critical regulators in various biological processes. In the present study, we aimed to explore whether miR140-3p was involved in the underlying molecular mechanisms of small nucleolar RNA host gene 1 (SNHG1) in myocardial ischemia/reperfusion (I/R) injury. A mouse model of I/R injury and hypoxia-reoxygenation (H/R)-stimulated human umbilical vein endothelial cells (HUVECs) was used in this study. Cell proliferation was detected by MTT. The mRNA and protein levels of vascular endothelial growth factor (VEGF), VE-cadherin, and MMP2 were detected by RT-PCR and western blot, respectively. The angiogenesis was assessed by tube formation assay. Cell migration was assessed using wound-healing assay. Results showed that SNHG1 expression was increased in the cardiac microvasculature of a mouse model of I/R injury and in H/R-stimulated HUVECs. H/R stimulation significantly reduced cell proliferation, tube formation, and cell migration, but increased expression of VEGF, VE-cadherin, and MMP2. SNHG1 upregulation under H/R increased HUVECs proliferation, tube formation, and cell migration, and upregulated expression of VEGF, VE-cadherin, and MMP2, compared with the H/R group. SNHG1 knockdown exhibited the opposite effect. SNHG1 functioned as a competing endogenous RNA (ceRNA) of miR-140-3p. HIF-1α was identified as a target of miR-140-3p. SNHG1 upregulation enhanced cell proliferation, tube formation, and expression of VEGF, VE-cadherin, and MMP2 through HIF-1α/VEGF signaling. This process could be offset by miR-140-3p mimic or VEGF inhibitor. Our results reveal a novel protective function of SNHG1 that furthers understanding of cardiac I/R injury and provides experimental evidence for future therapy.