Long non-coding RNA PVT1 regulates atherosclerosis progression via the microRNA-106b-5p/ACSL4 axis

Biochem Biophys Res Commun. 2023 Jul 30:667:170-179. doi: 10.1016/j.bbrc.2023.05.037. Epub 2023 May 13.

Abstract

Long non-coding RNAs (lncRNAs) have been associated with atherosclerosis (AS), but the role of lncRNA PVT1 in this disease is still unknown. However, lncRNA PVT1 was found to be significantly upregulated in the serum of AS patients. In vitro experiments using human vascular endothelial cells (HUVECs) showed that oxidized low-density lipoprotein (ox-LDL) treatment enhanced PVT1 expression and impeded HUVEC proliferation, which could be reversed by PVT1 knockdown or miR-106b-5p mimics. Additionally, knockdown of PVT1 and overexpression of miR-106b-5p inhibited the increase of iron content, MDA level, lipid ROS, ACSL4, and PTGS2 in ox-LDL-induced HUVECs, as well as the decrease of GSH and GPX4. We also found that PVT1 knockdown reduced lipid deposition, atherosclerotic plaque number, and size in ApoE-/- mice. These results suggest that PVT1 plays a crucial role in AS progression by regulating the miR-106b-5p/ACSL4 axis in HUVECs, and may therefore be a potential therapeutic target for AS.

Keywords: ACSL4; Atherosclerosis; Ferroptosis; LncRNA PVT1; miR-106b-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Atherosclerosis* / genetics
  • Atherosclerosis* / metabolism
  • Cell Proliferation
  • Coenzyme A Ligases / metabolism
  • Endothelial Cells / metabolism
  • Humans
  • Lipoproteins, LDL / metabolism
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / metabolism

Substances

  • Acsl4 protein, mouse
  • Coenzyme A Ligases
  • Lipoproteins, LDL
  • MicroRNAs
  • RNA, Long Noncoding
  • PVT1 long-non-coding RNA, human