miR-27b inhibits LDLR and ABCA1 expression but does not influence plasma and hepatic lipid levels in mice

Atherosclerosis. 2015 Dec;243(2):499-509. doi: 10.1016/j.atherosclerosis.2015.09.033.


Rationale: Recently, there has been significant interest in the therapeutic administration of miRNA mimics and inhibitors to treat cardiovascular disease. In particular, miR-27b has emerged as a regulatory hub in cholesterol and lipid metabolism and potential therapeutic target for treating atherosclerosis. Despite this, the impact of miR-27b on lipid levels in vivo remains to be determined. As such, here we set out to further characterize the role of miR-27b in regulating cholesterol metabolism in vitro and to determine the effect of miR-27b overexpression and inhibition on circulating and hepatic lipids in mice.

Methods and results: Our results identify miR-27b as an important regulator of LDLR activity in human and mouse hepatic cells through direct targeting of LDLR and LDLRAP1. In addition, we report that modulation of miR-27b expression affects ABCA1 protein levels and cellular cholesterol efflux to ApoA1 in human hepatic Huh7 cells. Overexpression of pre-miR-27b in the livers of wild-type mice using AAV8 vectors increased pre-miR-27b levels 50-fold and reduced hepatic ABCA1 and LDLR expression by 50% and 20%, respectively, without changing circulating and hepatic cholesterol and triglycerides. To determine the effect of endogenous miR-27b on circulating lipids, wild-type mice were fed a Western diet for one month and injected with 5 mg/kg of LNA control or LNA anti-miR-27b oligonucleotides. Following two weeks of treatment, the expression of ABCA1 and LDLR were increased by 10-20% in the liver, demonstrating effective inhibition of miR-27b function. Intriguingly, no differences in circulating and hepatic lipids were observed between treatment groups.

Conclusions: The results presented here provide evidence that short-term modulation of miR-27b expression in wild-type mice regulates hepatic LDLR and ABCA1 expression but does not influence plasma and hepatic lipid levels.

Keywords: ABCA1; Atherosclerosis; LDLR; Lipid homeostasis; miR-27b; miRNAs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • ATP Binding Cassette Transporter 1 / genetics
  • ATP Binding Cassette Transporter 1 / metabolism*
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Biomarkers / blood
  • COS Cells
  • Chlorocebus aethiops
  • Cholesterol / blood*
  • Computational Biology
  • Databases, Genetic
  • Diet, High-Fat*
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Hep G2 Cells
  • Humans
  • Liver / metabolism*
  • Macaca mulatta
  • Male
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Receptors, LDL / genetics
  • Receptors, LDL / metabolism*
  • Time Factors
  • Transfection
  • Triglycerides / blood


  • 3' Untranslated Regions
  • ABCA1 protein, human
  • ABCA1 protein, mouse
  • ATP Binding Cassette Transporter 1
  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • LDLR protein, human
  • LDLRAP1 protein, human
  • MIRN27 microRNA, human
  • MicroRNAs
  • Mirn27 microRNA, mouse
  • Receptors, LDL
  • Triglycerides
  • Cholesterol