Deletion of the Mir-106b~ 25 MicroRNA cluster attenuates atherosclerosis in Apolipoprotein E knockout mice

Lipids Health Dis. 2019 Dec 3;18(1):208. doi: 10.1186/s12944-019-1155-8.


Background: MicroRNAs are short non-coding RNAs that regulate gene expression. The aim of this study was to gain an understanding of the possible role of the miR-106b~ 25 microRNA cluster in regulating atherosclerosis in mice.

Methods: MiR-106b~ 25 knockout mice were outcrossed into Apolipoprotein E (ApoE) knockout background to generate double knockout mice. At 36 weeks of age, lesion size was evaluated in the aortic sinus by oil-red-O staining.

Results: Lesion size was 2-fold smaller in double KO mice in comparison to ApoE KO mice. In addition, collagen staining showed a trend towards a stable plaque phenotype in the double KO mice. Lipid profiling of plasma samples of double KO and ApoE KO mice using FPLC revealed over 2-fold decrease in Very low density lipoprotein (VLDL) cholesterol content and a 50% decrease in low density lipoprotein (LDL) cholesterol content in double KO mice. By using target prediction software, we have identified several possible targets for the miR-106b~ 25 cluster including the VLDL and LDL receptors. We found that upon feeding miR-106b~ 25 KO mice with high fat diet, the expression of LDL and VLDL receptors was higher than in the wild-type mice, suggesting the miR-106b~ 25 cluster regulates atherosclerosis by influencing clearance of VLDL and LDL from the plasma.

Conclusions: We identified the miR-106b~ 25 cluster as a novel regulator of atherosclerosis in ApoE KO mice, presumably by regulating plasma cholesterol levels.

Keywords: Atherosclerosis; Cholesterol; MicroRNAs.

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Aorta / pathology
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics*
  • Atherosclerosis / genetics*
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Base Sequence
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Cholesterol, VLDL / blood
  • Diet, High-Fat / methods
  • Dietary Fats / administration & dosage
  • Gene Expression
  • Male
  • Mice
  • Mice, Knockout
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Multigene Family
  • Plaque, Atherosclerotic / genetics*
  • Plaque, Atherosclerotic / metabolism
  • Plaque, Atherosclerotic / pathology
  • Receptors, LDL / genetics*
  • Receptors, LDL / metabolism
  • Sequence Deletion


  • Apolipoproteins E
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Cholesterol, VLDL
  • Dietary Fats
  • MicroRNAs
  • Mirn106 microRNA, mouse
  • Receptors, LDL
  • VLDL receptor