Profiling and functional analysis of differentially expressed circular RNAs in high glucose-induced human umbilical vein endothelial cells
Profiling and functional analysis of differentially expressed circular RNAs in high glucose-induced human umbilical vein endothelial cells
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DOI：
10.1002/2211-5463.12709
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发表时间：
2019-08-22
期刊：
影响因子：
2.6
通讯作者：
Li, Minglong
中科院分区：
文献类型：
--
作者：
Jin, Guoxi;Wang, Qiong;Li, Minglong
血管内皮细胞功能障碍常常导致糖尿病血管并发症。环状RNA（circRNA）与多种疾病的发病机制有关，包括糖尿病和许多血管疾病。本研究旨在探讨circRNA在高糖诱导的人脐静脉内皮细胞（HUVEC）中的作用，以阐明circRNA对糖尿病血管并发症的贡献。我们对对照和高葡萄糖诱导的 HUVEC 进行 RNA 测序，并鉴定了 214 个差异表达的 circRNA（与对照 HUVEC 相比，倍数变化 >= 2.0，P < 0.05）。然后，我们通过 qPCR 验证了其中 7 个差异表达的 circRNA（hsa_circ_0008360、hsa_circ_0005741、hsa_circ_0003250、hsa_circ_0045462、hsa_circ_0064772、hsa_circ_0007976 和 hsa_circ_0005263）。使用三种最上调的 circRNA（hsa_circ_0008360、hsa_circ_0000109 和 hsa_circ_0002317）及其推定的 miRNA 构建了代表性的 circRNA-microRNA (miRNA) 网络。生物信息分析表明，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。我们的工作强调了三种关键 circRNA 在糖尿病相关内皮功能障碍中的潜在调节机制。
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.