Abstract
Dysfunction of vascular endothelial cells often results in diabetic vascular complications. Circular RNAs (circRNAs) have been implicated in the pathogenesis of various diseases, including diabetes and many vascular diseases. This study aimed to explore the roles of circRNAs in high glucose‐induced human umbilical vein endothelial cells (HUVECs) to elucidate the contributions of circRNAs to diabetic vascular complications. We subjected control and high glucose‐induced HUVECs to RNA sequencing and identified 214 differentially expressed circRNAs (versus control HUVECs, fold change ≥ 2.0, P < 0.05). We then validated seven of these differentially expressed circRNAs by qPCR (hsa_circ_0008360, hsa_circ_0005741, hsa_circ_0003250, hsa_circ_0045462, hsa_circ_0064772, hsa_circ_0007976, and hsa_circ_0005263). A representative circRNA–microRNA (miRNA) network was constructed using the three most up‐regulated circRNAs (hsa_circ_0008360, hsa_circ_0000109, and hsa_circ_0002317) and their putative miRNA. Bioinformatic analysis indicated that these circRNAs regulate the expressions of genes involved in vascular endothelial function and angiogenesis through targeting miRNAs. Our work highlights the potential regulatory mechanisms of three crucial circRNAs in diabetes‐associated endothelial dysfunction.
Highlights
Dysfunction of vascular endothelial cells often results in diabetic vascular complications
In order to characterize the landscape of circRNA expression, we performed deep RNA-seq experiments using three normal human umbilical vein endothelial cells (HUVECs) samples and three high glucose-induced HUVECs samples
We identified 17 418 circRNAs from six samples, and 6468 circRNAs were detected in both control and high glucose-induced groups (Fig. 1A)
Summary
Dysfunction of vascular endothelial cells often results in diabetic vascular complications. This study aimed to explore the roles of circRNAs in high glucoseinduced human umbilical vein endothelial cells (HUVECs) to elucidate the contributions of circRNAs to diabetic vascular complications. Abbreviations CircRNAs, circular ribonucleic acid; GO, Gene Ontology; HUVECs, human umbilical vein endothelial cells; KEGG, Kyoto Encyclopedia of Genes and Genomes; MF, molecular function; miRNA, microRNA; MREs, miRNA response elements; NF-kB, nuclear factor kappa B; QC, quality control; T2DM, type 2 diabetes mellitus; VEGF, vascular endothelial growth factor. Since circRNAs have been found to be widely involved in atherosclerotic vascular disease [20] and diabetes [21,22], it is interesting to explore the effect of high glucose-induced dysfunction of circRNAs on vascular endothelial cells. Up to now, there are few studies that have systematically investigated the alterations of global circRNA expression in high glucoseinduced HUVECs
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