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Profiling and functional analysis of differentially expressed circular RNAs in high glucose‐induced human umbilical vein endothelial cells

机译:高糖诱导的人脐静脉内皮细胞中差异表达的环状RNA的分析和功能分析

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摘要

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.
机译:血管内皮细胞功能障碍常导致糖尿病性血管并发症。环状RNA(circRNA)已与多种疾病的发病机制有关,包括糖尿病和许多血管疾病。这项研究旨在探讨circRNA在高糖诱导的人脐静脉内皮细胞(HUVEC)中的作用,以阐明circRNA在糖尿病血管并发症中的作用。我们对对照和高葡萄糖诱导的HUVEC进行了RNA测序,并鉴定了214种差异表达的circRNA(相对于对照HUVEC,倍数变化≥2.0,P <0.05)。然后,我们通过qPCR验证了这些差异表达的circRNA中的七个(hsa_circ_0008360,hsa_circ_0005741,hsa_circ_0003250,hsa_circ_0045462,hsa_circ_0064772,hsa_circ_0007976和hsa_circ_0005263)。使用三个上调最多的circRNA(hsa_circ_0008360,hsa_circ_0000109和hsa_circ_0002317)及其推定的miRNA构建了一个代表性的circRNA-microRNA(miRNA)网络。生物信息学分析表明,这些circRNA通过靶向miRNA来调节参与血管内皮功能和血管生成的基因的表达。我们的工作强调了糖尿病相关内皮功能障碍中三种关键circRNA的潜在调控机制。

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