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Science. 2010 Jun 18;328(5985):1566-9. doi: 10.1126/science.1189123. Epub 2010 May 13.

MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis.

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1
Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.

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.

PMID:
20466882
PMCID:
PMC3840500
DOI:
10.1126/science.1189123
[Indexed for MEDLINE]
Free PMC Article

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