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

Hani Najafi, Fjoralba Kristo, Yingxia Li, Toshi Shioda, David E. Cohen, Robert E. Gerszten, Anders M. Näär

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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 westerntype 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. Copyright Science 2010 by the American Association for the Advancement of Science; all rights reserved.

Original languageEnglish
Pages (from-to)1566-1569
Number of pages4
JournalScience
Volume328
Issue number5985
DOIs
Publication statusPublished - 18 Jun 2010
Externally publishedYes

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Cite this

Najafi, H., Kristo, F., Li, Y., Shioda, T., Cohen, D. E., Gerszten, R. E., & Näär, A. M. (2010). MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science, 328(5985), 1566-1569. https://doi.org/10.1126/science.1189123