Document Detail

MicroRNA-223 coordinates cholesterol homeostasis.
MedLine Citation:
PMID:  25246565     Owner:  NLM     Status:  Publisher    
MicroRNAs (miRNAs) regulate a wide variety of biological processes and contribute to metabolic homeostasis. Here, we demonstrate that microRNA-223 (miR-223), an miRNA previously associated with inflammation, also controls multiple mechanisms associated with cholesterol metabolism. miR-223 promoter activity and mature levels were found to be linked to cellular cholesterol states in hepatoma cells. Moreover, hypercholesterolemia was associated with increased hepatic miR-223 levels in athero-prone mice. miR-223 was found to regulate high-density lipoprotein-cholesterol (HDL-C) uptake, through direct targeting and repression of scavenger receptor BI, and to inhibit cholesterol biosynthesis through the direct repression of sterol enzymes 3-hydroxy-3-methylglutaryl-CoA synthase 1 and methylsterol monooxygenase 1 in humans. Additionally, miR-223 was found to indirectly promote ATP-binding cassette transporter A1 expression (mRNA and protein) through Sp3, thereby enhancing cellular cholesterol efflux. Finally, genetic ablation of miR-223 in mice resulted in increased HDL-C levels and particle size, as well as increased hepatic and plasma total cholesterol levels. In summary, we identified a critical role for miR-223 in systemic cholesterol regulation by coordinated posttranscriptional control of multiple genes in lipoprotein and cholesterol metabolism.
Kasey C Vickers; Stuart R Landstreet; Michael G Levin; Bassem M Shoucri; Cynthia L Toth; Robert C Taylor; Brian T Palmisano; Fatiha Tabet; Huanhuan L Cui; Kerry-Anne Rye; Praveen Sethupathy; Alan T Remaley
Related Documents :
25197505 - The effect of weight reduction on ultrasonographic findings of nonalcoholic fatty liver.
2021125 - Nutritional determinants of the increase in energy intake associated with a high-fat diet.
11584105 - Carbohydrates, appetite and feeding behavior in humans.
2124925 - The initial physiological responses to glucose ingestion in normal subjects are modifie...
22662175 - Oligonucleotide microarray analysis of dietary-induced hyperlipidemia gene expression p...
14974565 - Effects of endophyte-infected tall fescue on indicators of thermal status and growth in...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-22
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  -     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-23     Completed Date:  -     Revised Date:  2014-9-24    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Platelet mechanosensing of substrate stiffness during clot formation mediates adhesion, spreading, a...
Next Document:  Scaling description of the yielding transition in soft amorphous solids at zero temperature.