LncRNA LEF1-AS1 regulates the migration and proliferation of vascular smooth muscle cells by targeting miR-544a/PTEN axis

J Cell Biochem. 2019 Sep;120(9):14670-14678. doi: 10.1002/jcb.28728. Epub 2019 Apr 23.

Abstract

Long noncoding RNAs (lncRNAs) play important roles in endothelium development. A lncRNA, LEF1-AS1, is recently emerging as a potent mediator of the proliferation and migration of a number of cells, including smooth muscle cells. However, the effects of LEF1-AS1 in atherosclerosis remains largely unknown. Specimens from patients with coronary artery atherosclerosis were collected. The quantitative real-time polymerase chain reaction was used to analyze levels of LEF1-AS1 and microRNA-544a (miR-544a). Western blot analysis was used to assess PTEN, P-Akt, and T-Akt protein expression. Proliferation, migration, and invasion of cells were analyzed by cell counting kit-8 assay, scratch wound assay, and transwell assay, respectively. The interaction between LEF1-AS1, miR-544a, and PTEN was probed using bioinformatical analysis and dual-luciferase assay. In plasma and tissue of patients with coronary artery atherosclerosis, LEF1-AS1 was upregulated and miR-544a was downregulated. A negative correlation was found between LEF1-AS1 and miR-544a. miR-544a overexpression reversed the inhibition of LEF1-AS1 in smooth muscle cell proliferation and invasion, which were mediated through the PTEN pathway. LEF1-AS1 regulates smooth muscle cell proliferation and migration through the miR-544a/PTEN axis, indicating that LEF1-AS1 may be a potential therapeutic target in atherosclerosis.

Keywords: LEF1-AS1; atherosclerosis; long noncoding RNA; miR-544a/PTEN axis; vascular smooth muscle cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology*
  • Case-Control Studies
  • Cell Movement*
  • Cell Proliferation*
  • Cells, Cultured
  • Coronary Artery Disease / genetics
  • Coronary Artery Disease / metabolism
  • Coronary Artery Disease / pathology*
  • Gene Expression Regulation
  • Humans
  • Lymphoid Enhancer-Binding Factor 1 / antagonists & inhibitors
  • MicroRNAs / genetics*
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / metabolism
  • Oligonucleotides, Antisense / genetics
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • Prognosis
  • RNA, Long Noncoding / genetics*

Substances

  • LEF1 protein, human
  • Lymphoid Enhancer-Binding Factor 1
  • MIRN544 microRNA, human
  • MicroRNAs
  • Oligonucleotides, Antisense
  • RNA, Long Noncoding
  • PTEN Phosphohydrolase
  • PTEN protein, human