Human circular RNA-0054633 regulates high glucose-induced vascular endothelial cell dysfunction through the microRNA-218/roundabout 1 and microRNA-218/heme oxygenase-1 axes

The aim of the present study was to investigate the relative regulation of human circular RNA-0054633 (hsa_circ_0054633), microRNA-218 (miR-218), roundabout 1 (ROBO1) and heme oxygenase-1 (HO-1) in human umbilical vein endothelial cells (HUVECs) in high glucose conditions. Initially, the expression of hsa_circ_0054633 in HUVECs was detected in high glucose conditions by reverse transcription-quantitative polymerase chain reaction. Next, a small interfering RNA against hsa_circ_0054633 was constructed to investigate the function of jsa_circ_0054633 in HUVECs by transwell migration, cell counting kit-8, flow cytometry and tube formation assays. In addition, the effect of hsa_circ_0054633 on the expression levels of ROBO1, HO-1 and vascular endothelial growth factor were examined. The regulation effects of hsa_circ_0054633 on high glucose-induced HUVEC proliferation, migration, and angiopoiesis were also analyzed. Bioinformatics analysis and dual-luciferase assay were then used to confirm the direct or specific regulation of hsa_circ_0054633, miR-218, ROBO1 and HO-1. It was observed that high glucose levels increased the expression of hsa_circ_0054633, while downregulation of hsa_circRNA-0054633 increased the high glucose-induced endothelial cell dysfunction, including proliferation, migration and angiopoiesis suppression. Bioinformatics analysis revealed that the expression of circRNA-0054633 was able to inhibit miR-218 expression, which was clarified by the dual-luciferase assay. It was also demonstrated that downregulating the expression of miR-218 inhibited the high glucose-induced endothelial cell dysfunction by promoting the expression of ROBO1 and HO-1. These results suggest that the expression of hsa_circRNA-0054633 has a protective effect against high glucose-induced endothelial cell dysfunction by targeting ROBO1 and HO-1.