miR-467b regulates the cholesterol ester formation via targeting ACAT1 gene in RAW 264.7 macrophages

Biochimie. 2017 Jan:132:38-44. doi: 10.1016/j.biochi.2016.09.012. Epub 2016 Sep 24.

Abstract

Previous studies have shown that miR-467b plays a central role in the progression of atherosclerosis via regulating LPL expression. However, the regulatory mechanism of miR-467b in regulateing the CE and FC formation is still unclear. Interestingly, computational analysis demonstrated that ACAT1 which converts intracellular FC into the storage form of CE, and ABCA1 which promotes cellular FC efflux may be target gene of miR-467b. Here, we examined whether miR-467b could target ACAT1 and ABCA1, thereby affecting the CE and FC formation in oxLDL-treatment RAW 264.7 cells. We found that miR-467b regulates the CE:FC ratio in oxLDL-treatment RAW 264.7 macrophages, and the luciferase activity of ACAT1 is regulated by the miR-467b, but the luciferase activity of ABCA1 has no effect. Furthermore, our data suggested that miR-467b highly regulates the endogenous levels of ACAT1 expression, thereby affecting the CE formation in oxLDL-treatment RAW 264.7 macrophages. Taken together, our findings demonstrate that ACAT1 is a target gene of miR-467b, and miR-467b regulated the CE and FC formation via directly target the ACAT1 3'UTR.

Keywords: ABCA1; ACAT1; Atherosclerosis; CE:FC ratio; miR-467b.

MeSH terms

  • 3' Untranslated Regions / genetics
  • ATP Binding Cassette Transporter 1 / genetics
  • ATP Binding Cassette Transporter 1 / metabolism
  • Acetyl-CoA C-Acetyltransferase / genetics*
  • Acetyl-CoA C-Acetyltransferase / metabolism
  • Animals
  • Blotting, Western
  • Cell Line
  • Cholesterol / metabolism
  • Cholesterol Esters / metabolism*
  • Gene Expression Regulation*
  • Lipoproteins, LDL / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Mice
  • MicroRNAs / genetics*
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • 3' Untranslated Regions
  • ABCA1 protein, mouse
  • ATP Binding Cassette Transporter 1
  • Cholesterol Esters
  • Lipoproteins, LDL
  • MIRN467 microRNA, mouse
  • MicroRNAs
  • oxidized low density lipoprotein
  • Cholesterol
  • Acat1 protein, mouse
  • Acetyl-CoA C-Acetyltransferase