Hsa_circ_0008360 sponges miR-186-5p to target CCND2 to modulate high glucose-induced vascular endothelial dysfunction

• Published in: Cell cycle (Georgetown, Tex.) Vol. 20; no. 14; pp. 1389 - 1401
• Main Authors: Zhu, Qian-Qian, Pu, Xi-Bin, Chen, Tian-Chi, Qiu, Chen-Yang, Wu, Zi-Heng, Tian, Lu, He, Yang-Yan, Wang, Xiao-Hui, Shang, Tao, Wang, Xun, Xiang, Yi-Lang, Li, Dong-Lin, Zhang, Hong-Kun
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.07.2021
• Subjects: Apoptosis - genetics; Cell Proliferation - genetics; Cyclin D2 - genetics; Glucose - pharmacology; Humans; MicroRNAs - metabolism; Research Paper; RNA, Circular - genetics; Vascular endothelial dysfunction; circ_0008360; CCND2; miR-186-5p; high glucose
• ISSN: 1538-4101; 1551-4005
• DOI: 10.1080/15384101.2021.1918877

Vascular endothelial dysfunction is associated with the progress of many diseases. Circular RNAs (circRNAs) take part in the dysfunction of vascular endothelium. CircRNA hsa_circ_0008360 (circ_0008360) is dysregulated in high glucose-treated vascular endothelium, while the role and mechanism of circ_0008360 in high glucose-induced dysfunction remain unknown. Human umbilical vascular endothelium cells (HUVEC) were stimulated via high glucose. The abundances of circ_0008360, miR-186-5p and cyclin D2 (CCND2) were examined via quantitative real-time polymerase chain reaction or western blot. Vascular endothelial dysfunction was assessed via cell viability, apoptosis, migration and tube formation. The target relationship between miR-186-5p and circ_0008360 or CCND2 was analyzed via dual-luciferase reporter, RNA pull-down and RNA immunoprecipitation analyses. Circ_0008360 expression was enhanced in high-glucose-treated HUVEC. Circ_0008360 silence mitigated high glucose-induced suppression of viability, migration, tube formation, and increase in apoptosis in HUVEC. MiR-186-5p was sponged by circ_0008360, and miR-186-5p inhibition reversed the effect of circ_0008360 silence on high glucose-induced vascular endothelial dysfunction. MiR-186-5p alleviated high glucose-induced vascular endothelial dysfunction via targeting CCND2. CCND2 interference abolished the aggravated effect of circ_0008360 on high glucose-induced vascular endothelial dysfunction. Circ_0008360 knockdown attenuated high glucose-induced vascular endothelial dysfunction via regulating miR-186-5p and CCND2, indicating circ_0008360 might act as a target for the treatment of vascular endothelial dysfunction. circRNAs, circular RNAs; HUVEC, human umbilical vascular endothelium cells; CCND2, cyclin D2; XPNPEP3, X-prolyl aminopeptidase 3; ceRNAs, competing endogenous RNAs; miRNAs, microRNAs; qRT-PCR, quantitative real-time polymerase chain reaction; RIP, RNA immunoprecipitation; HIF-1α, hypoxia inducible factor 1 alpha; TLR3, toll-like receptor 3; AKAP12, A-Kinase Anchoring Protein 12; ox-LDL, oxidized low-density lipoprotein; HG, high glucose; NG, normal glucose.