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

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.

Circ_CLASP2 Regulates High Glucose-Induced Dysfunction of Human Endothelial Cells Through Targeting miR-140-5p/FBXW7 Axis

“…It was reported that circ_CLASP2 expression was prominently decreased in HUVECs under HG exposure (Jin, Wang, 2019). To validate this, we used HG to treat HUVECs for various time points, and our data supported the downregulation of circ-CLASP2 in HG-treated HUVECs.…”

“…Hence, it is very crucial to identify effective biomarkers for the detection of ECs dysfunction and the prevention of macrovascular complications. One promising biomarker is based on circular RNAs (circRNAs) ( Shang et al, 2018 ; Jin et al, 2019 ).…”

“…Up to now, some circRNAs have been proposed to act as critical regulators in gene expression via functioning as microRNAs (miRNAs) sponges ( Granados-Riveron and Aquino-Jarquin, 2016 ). The abnormal expression and role of circRNAs in ECs dysfunction induced by high glucose (HG) have been widely investigated ( Liu et al, 2017 ; Pei et al, 2018 ; Shang et al, 2018 ; Jin et al, 2019 ; Zhang and Sui, 2020 ). For example, Cheng et al highlighted that has_circ_0068087 was highly expressed in HG-triggered human umbilical vein endothelial cells (HUVECs) and regulated HG-induced cell dysfunction by acting as an miR-197 sponge ( Cheng et al, 2019 ).…”

Comprehensive Analysis of Differentially Expressed Profiles of circRNAs in Diabetic Cardiomyopathy

“…CircRNAs are a widespread RNA species in various species and have important biological functions. They are involved in the regulation of islet cell function and insulin metabolism [18], also mediate vascular damage caused by high glucose as well [19,20].…”

Circular RNA and its mechanisms in diabetic retinopathy: a systematic review

“…Shang et al 24 reported that more than 1,000 new circRNAs and 95 differentially expressed circRNAs were detected in HUVEC cultured in high glucose environment in vitro. Jin et al 25 identified 214 differentially expressed circRNAs in high glucose induced HUVEC compared with normal controls by using RNA sequencing, of which 7 were validated using qPCR (hsa_circ_0008360, hsa_circ_0005741, hsa_circ_0003250, hsa_circ_0045462, hsa_circ_0064772, hsa_circ_0007976 and hsa_circ_0005263). Huang et al 26 reported that in rat HAEC induced by transforming growth factor β1 (TGF-β1), a total of 102 circRNA was differentially expressed, of which 66 circRNA expressions were up-regulated and 26 circRNA expressions were down-regulated.…”