Titre
Regulation of fibrinogen production by microRNAs.
Type
article
Institution
Externe
Périodique
Auteur(s)
Fort, A.
Auteure/Auteur
Borel, C.
Auteure/Auteur
Migliavacca, E.
Auteure/Auteur
Antonarakis, S.E.
Auteure/Auteur
Fish, R.J.
Auteure/Auteur
Neerman-Arbez, M.
Auteure/Auteur
Liens vers les personnes
ISSN
1528-0020[electronic], 0006-4971[linking]
Statut éditorial
Publié
Date de publication
2010
Volume
116
Numéro
14
Première page
2608
Dernière page/numéro d’article
2615
Langue
anglais
Résumé
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.
PID Serval
serval:BIB_436A1548B893
PMID
Open Access
Oui
Date de création
2010-12-15T09:43:04.134Z
Date de création dans IRIS
2025-05-20T15:04:05Z