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

Research output: Contribution to journalArticle

609 Citations (Scopus)

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

Fingerprint

Sterol Regulatory Element Binding Proteins
MicroRNAs
Homeostasis
Cholesterol
Genes
HDL Lipoproteins
Adenosine Triphosphate
Antisense Oligonucleotides
Regulator Genes
Introns
Up-Regulation
Diet
Cell Line
Injections
Health

ASJC Scopus subject areas

  • General

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

MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. / Najafi, Hani; Kristo, Fjoralba; Li, Yingxia; Shioda, Toshi; Cohen, David E.; Gerszten, Robert E.; Näär, Anders M.

In: Science, Vol. 328, No. 5985, 18.06.2010, p. 1566-1569.

Research output: Contribution to journalArticle

Najafi, H, Kristo, F, Li, Y, Shioda, T, Cohen, DE, Gerszten, RE & Näär, AM 2010, 'MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis', Science, vol. 328, no. 5985, pp. 1566-1569. https://doi.org/10.1126/science.1189123
Najafi H, Kristo F, Li Y, Shioda T, Cohen DE, Gerszten RE et al. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science. 2010 Jun 18;328(5985):1566-1569. https://doi.org/10.1126/science.1189123
Najafi, Hani ; Kristo, Fjoralba ; Li, Yingxia ; Shioda, Toshi ; Cohen, David E. ; Gerszten, Robert E. ; Näär, Anders M. / MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. In: Science. 2010 ; Vol. 328, No. 5985. pp. 1566-1569.
@article{ad6051fe982f4c54acc3b7d158c4df38,
title = "MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis",
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.",
author = "Hani Najafi and Fjoralba Kristo and Yingxia Li and Toshi Shioda and Cohen, {David E.} and Gerszten, {Robert E.} and N{\"a}{\"a}r, {Anders M.}",
year = "2010",
month = "6",
day = "18",
doi = "10.1126/science.1189123",
language = "English",
volume = "328",
pages = "1566--1569",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "5985",

}

TY - JOUR

T1 - MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis

AU - Najafi, Hani

AU - Kristo, Fjoralba

AU - Li, Yingxia

AU - Shioda, Toshi

AU - Cohen, David E.

AU - Gerszten, Robert E.

AU - Näär, Anders M.

PY - 2010/6/18

Y1 - 2010/6/18

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77953780835&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953780835&partnerID=8YFLogxK

U2 - 10.1126/science.1189123

DO - 10.1126/science.1189123

M3 - Article

C2 - 20466882

AN - SCOPUS:77953780835

VL - 328

SP - 1566

EP - 1569

JO - Science

JF - Science

SN - 0036-8075

IS - 5985

ER -