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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 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.

SUBMITTER: Najafi-Shoushtari SH 

PROVIDER: S-EPMC3840500 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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

Najafi-Shoushtari S Hani SH   Kristo Fjoralba F   Li Yingxia Y   Shioda Toshi T   Cohen David E DE   Gerszten Robert E RE   Näär Anders M AM  

Science (New York, N.Y.) 20100513 5985


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,  ...[more]

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