Regulation of fibrinogen production by microRNAs.

Details

Serval ID
serval:BIB_436A1548B893
Type
Article: article from journal or magazin.
Collection
Publications
Title
Regulation of fibrinogen production by microRNAs.
Journal
Blood
Author(s)
Fort A., Borel C., Migliavacca E., Antonarakis S.E., Fish R.J., Neerman-Arbez M.
ISSN
1528-0020[electronic], 0006-4971[linking]
Publication state
Published
Issued date
2010
Volume
116
Number
14
Pages
2608-2615
Language
english
Abstract
Elevated levels of fibrinogen are associated with increased risk of cardiovascular disease, whereas low fibrinogen can lead to a bleeding disorder. We investigated whether microRNAs (miRNAs), known to act as post-transcriptional regulators of gene expression, regulate fibrinogen production. Using transfection of a library of 470 annotated human miRNA precursor molecules in HuH7 hepatoma cells and quantitative measurements of fibrinogen production, we identified 23 miRNAs with down-regulating (up to 64% decrease) and 4 with up-regulating effects (up to 129% increase) on fibrinogen production. Among the down-regulating miRNAs, we investigated the mechanism of action of 3 hsa-miR-29 family members and hsa-miR-409-3p. Overexpression of hsa-miR-29 members led to decreased steady-state levels of all fibrinogen gene (FGA, FGB, and FGG) transcripts in HuH7 cells. Luciferase reporter gene assays demonstrated that this was independent of miRNA-fibrinogen 3'-untranslated region interactions. In contrast, overexpression of hsa-miR-409-3p specifically lowered fibrinogen B? mRNA levels, and this effect was dependent on a target site in the fibrinogen B? mRNA 3'-untranslated region. This study adds to the known mechanisms that control fibrinogen production, points toward a potential cause of variable circulating fibrinogen levels, and demonstrates that a screening approach can identify miRNAs that regulate clinically important proteins.
Keywords
3' Untranslated Regions, Cell Line, Cell Line, Tumor, Fibrinogen/genetics, Fibrinogen/metabolism, Gene Expression Regulation, Genes, Reporter, Humans, MicroRNAs/genetics
Pubmed
Open Access
Yes
Create date
15/12/2010 10:43
Last modification date
20/08/2019 13:47
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