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MicroRNA-33 and the SREBP Host Genes Cooperate to Control Cholesterol Homeostasis
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MicroRNA-33 and the SREBP Host Genes Cooperate to Control Cholesterol Homeostasis
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Journal Article
MicroRNA-33 and the SREBP Host Genes Cooperate to Control Cholesterol Homeostasis
2010
Overview
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.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
/ Animals
/ ATP
/ ATP Binding Cassette Transporter 1
/ ATP-Binding Cassette Transporters - genetics
/ ATP-Binding Cassette Transporters - metabolism
/ Biological and medical sciences
/ Diet
/ Genes
/ Humans
/ Introns
/ Mice
/ MicroRNA
/ Oligonucleotides, Antisense - pharmacology
/ RNA
/ Sterol Regulatory Element Binding Protein 1 - genetics
/ Sterol Regulatory Element Binding Protein 1 - metabolism
/ Sterol Regulatory Element Binding Protein 2 - genetics
/ Sterol Regulatory Element Binding Protein 2 - metabolism
/ Sterol Regulatory Element Binding Proteins - genetics
