Publication Date:
2010-05-15
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3840500/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3840500/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Najafi-Shoushtari, S Hani -- Kristo, Fjoralba -- Li, Yingxia -- Shioda, Toshi -- Cohen, David E -- Gerszten, Robert E -- Naar, Anders M -- P30 DK034854/DK/NIDDK NIH HHS/ -- P30 DK34854/DK/NIDDK NIH HHS/ -- R01 DK048873/DK/NIDDK NIH HHS/ -- R01 DK056626/DK/NIDDK NIH HHS/ -- R01 GM071449/GM/NIGMS NIH HHS/ -- R01DK48873/DK/NIDDK NIH HHS/ -- R01DK56626/DK/NIDDK NIH HHS/ -- R01GM071449/GM/NIGMS NIH HHS/ -- R21 DK084459/DK/NIDDK NIH HHS/ -- R21DK084459/DK/NIDDK NIH HHS/ -- R37 DK048873/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2010 Jun 18;328(5985):1566-9. doi: 10.1126/science.1189123. Epub 2010 May 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20466882" target="_blank"〉PubMed〈/a〉
Keywords:
3' Untranslated Regions
;
ATP Binding Cassette Transporter 1
;
ATP-Binding Cassette Transporters/genetics/*metabolism
;
Animals
;
Cell Line
;
Cholesterol/*metabolism
;
Cholesterol, HDL/*blood
;
Diet
;
Gene Expression Regulation
;
Homeostasis
;
Humans
;
Introns
;
Liver/metabolism
;
Macrophages/metabolism
;
Mice
;
Mice, Inbred C57BL
;
MicroRNAs/genetics/*metabolism
;
Oligonucleotides, Antisense/pharmacology
;
RNA Interference
;
Sterol Regulatory Element Binding Protein 1/genetics/metabolism
;
Sterol Regulatory Element Binding Protein 2/genetics/metabolism
;
Sterol Regulatory Element Binding Proteins/*genetics/metabolism
;
Up-Regulation
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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