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Regulation of fibrinogen production by microRNAs

Migliavacca, Eugenia
Published in Blood. 2010, vol. 116, no. 14, p. 2608-2615
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 Bbeta mRNA levels, and this effect was dependent on a target site in the fibrinogen Bbeta 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 RegionsCell LineCell Line, TumorFibrinogen/*genetics/metabolism*Gene Expression RegulationGenes, ReporterHumansMicroRNAs/*genetics
PMID: 20570858
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Research groups Endothélium vasculaire (11)
Pathologie Moléculaire de la Trisomie 21 et le Génome Humain (248)
Recherche translationnelle : anomalies de l'hémostase et thromboses (504)
(ISO format)
FORT, Alexandre et al. Regulation of fibrinogen production by microRNAs. In: Blood, 2010, vol. 116, n° 14, p. 2608-2615. doi: 10.1182/blood-2010-02-268011 https://archive-ouverte.unige.ch/unige:20943

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Deposited on : 2012-05-23

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