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

Cell Cycle. 2021 Jul;20(14):1389-1401. doi: 10.1080/15384101.2021.1918877. Epub 2021 Jul 5.

Abstract

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.Abbreviations: 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.

Keywords: CCND2; Vascular endothelial dysfunction; circ_0008360; high glucose; miR-186-5p.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Apoptosis / genetics
  • Cell Proliferation / genetics
  • Cyclin D2 / genetics
  • Glucose / pharmacology
  • Humans
  • MicroRNAs* / metabolism
  • RNA, Circular* / genetics

Substances

  • CCND2 protein, human
  • Cyclin D2
  • MIRN186 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Glucose

Grants and funding

This study was sponsored by Major Science and Technology Project in Medical and Health of Zhejiang Province (co-constructed Project by Province and the Ministry, 2020380400, WKJ-ZJ-2003); Key R&D Program of Zhejiang province (Grant Code: 2019C03013); Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (Grant Code:2021KY155).