MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis Academic Article uri icon

Overview

MeSH Major

  • ATP-Binding Cassette Transporters
  • Cholesterol
  • Cholesterol, HDL
  • MicroRNAs
  • Sterol Regulatory Element Binding Proteins

abstract

  • Proper coordination of cholesterol biosynthesis and trafficking is essential to human health. The sterol regulatory element-binding proteins (SREBPs) are key transcription regulators of genes involved in cholesterol biosynthesis and uptake. We show here that microRNAs (miR-33a/b) embedded within introns of the SREBP genes target the adenosine triphosphate-binding cassette transporter A1 (ABCA1), an important regulator of high-density lipoprotein (HDL) synthesis and reverse cholesterol transport, for posttranscriptional repression. Antisense inhibition of miR-33 in mouse and human cell lines causes up-regulation of ABCA1 expression and increased cholesterol efflux, and injection of mice on a western-type diet with locked nucleic acid-antisense oligonucleotides results in elevated plasma HDL. Our findings indicate that miR-33 acts in concert with the SREBP host genes to control cholesterol homeostasis and suggest that miR-33 may represent a therapeutic target for ameliorating cardiometabolic diseases.

publication date

  • June 18, 2010

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3840500

Digital Object Identifier (DOI)

  • 10.1126/science.1189123

PubMed ID

  • 20466882

Additional Document Info

start page

  • 1566

end page

  • 9

volume

  • 328

number

  • 5985