Oxidized low-density lipoprotein accelerates the injury of endothelial cells via circ-USP36/miR-98-5p/VCAM1 axis

IUBMB Life. 2021 Jan;73(1):177-187. doi: 10.1002/iub.2419. Epub 2020 Nov 28.


Circular RNAs (circRNAs) are a group of RNAs featured by a covalently closed continuous loop structure. This study aimed to uncover the function and mechanism of circ-ubiquitin specific peptidase 36 (USP36) in endothelial cells treated with oxidized low-density lipoprotein (ox-LDL). The levels of circ-USP36, microRNA-98-5p (miR-98-5p) and vascular cell adhesion molecule 1 (VCAM1) were examined by a quantitative real-time polymerase chain reaction (qRT-PCR). The viability, apoptosis and inflammation were detected by (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. Western blot assay was performed to detect the expression of apoptosis and proliferation-related markers and VCAM1 protein level. The targets of circ-USP36 and miR-98-5p were searched using starBase website, and dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to validate the above predictions. Ox-LDL exposure induced the upregulation of circ-USP36 in HUVEC cells. Circ-USP36 accelerated ox-LDL-induced apoptosis, inflammatory and viability inhibition of HUVEC cells. MiR-98-5p was a direct downstream gene of circ-USP36. Circ-USP36 promoted the injury of ox-LDL-induced HUVEC cells through targeting miR-98-5p. VCAM1 could bind to miR-98-5p, and the protective effects of miR-98-5p accumulation on ox-LDL-induced HUVEC cells were reversed by the transfection of VCAM1. VCAM1 was regulated by circ-USP36/miR-98-5p signaling in HUVEC cells. Ox-LDL promoted the apoptosis and inflammation but suppressed the viability of HUVEC cells through upregulating circ-USP36, thus elevating the expression of VCAM1 via miR-98-5p.

Keywords: VCAM1; atherosclerosis; circ-USP36; endothelial cells; miR-98-5p; ox-LDL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Proliferation
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / injuries
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology*
  • Gene Expression Regulation
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Inflammation / chemically induced
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / pathology*
  • Lipoproteins, LDL / adverse effects*
  • MicroRNAs / genetics*
  • RNA, Circular / genetics*
  • Signal Transduction
  • Ubiquitin Thiolesterase / genetics*
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism*


  • Lipoproteins, LDL
  • MIRN98 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • USP36 protein, human
  • Vascular Cell Adhesion Molecule-1
  • oxidized low density lipoprotein
  • Ubiquitin Thiolesterase