The lncRNA MALAT1 protects the endothelium against ox-LDL-induced dysfunction via upregulating the expression of the miR-22-3p target genes CXCR2 and AKT

FEBS Lett. 2015 Oct 7;589(20 Pt B):3189-96. doi: 10.1016/j.febslet.2015.08.046. Epub 2015 Sep 10.

Abstract

CXCR2 plays a key role in protecting the integrity of the endothelium. Emerging evidence has demonstrated that the long ncRNAs (lncRNA) Human metastasis associated lung adenocarcinoma transcript 1 (MALAT1) participates in the regulation of the pathophysiological processes. However, whether there is crosstalk between CXCR2 and MALAT1 remains unknown. In this study, we demonstrated that MALAT1 was upregulated in patients with unstable angina. MALAT1 silencing significantly downregulated the expression of the miR-22-3p target gene CXCR2 via reversing the effect of the miR-22-3p, resulting in the aggravation of Oxidized low-density lipoprotein (ox-LDL)-induced endothelial injury; this process was associated with the AKT pathway. Thus, MALAT1 protects the endothelium from ox-LDL-induced endothelial dysfunction partly through competing with miR-22-3p for endogenous RNA.

Keywords: CXCR2; Endothelial cells; MALAT1; miRNA-22-3p; ox-LDL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angina, Unstable / genetics
  • Angina, Unstable / metabolism
  • Apoptosis / genetics
  • Base Sequence
  • Blotting, Western
  • Cells, Cultured
  • Gene Expression Regulation / drug effects
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Lipoproteins, LDL / pharmacology
  • MicroRNAs / genetics*
  • Models, Genetic
  • Proto-Oncogene Proteins c-akt / genetics*
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • Receptors, Interleukin-8B / genetics*
  • Receptors, Interleukin-8B / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Nucleic Acid
  • Signal Transduction / genetics
  • Up-Regulation / drug effects

Substances

  • Lipoproteins, LDL
  • MALAT1 long non-coding RNA, human
  • MIRN22 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Receptors, Interleukin-8B
  • oxidized low density lipoprotein
  • Proto-Oncogene Proteins c-akt