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

Pan,Long; Lian,Weishuai; Zhang,Xiaojun; Han,Shilong; Cao,Chuanwu; Li,Xue; Li,Maoquan

doi:10.3892/ijmm.2018.3625

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

Authors:
- Long Pan
- Weishuai Lian
- Xiaojun Zhang
- Shilong Han
- Chuanwu Cao
- Xue Li
- Maoquan Li
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Affiliations: Department of Interventional and Vascular Surgery, Tenth People's Hospital of Tongji University, Shanghai 200072, P.R. China
Published online on: April 16, 2018 https://doi.org/10.3892/ijmm.2018.3625
Pages: 597-606

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Abstract

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.

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