

Other version: http://bloodjournal.hematologylibrary.org/content/116/14/2608.full.pdf
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Regulation of fibrinogen production by microRNAs |
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Authors | ||
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 Regions — Cell Line — Cell Line, Tumor — Fibrinogen/*genetics/metabolism — *Gene Expression Regulation — Genes, Reporter — Humans — MicroRNAs/*genetics | |
Identifiers | PMID: 20570858 | |
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![]() ![]() Other version: http://bloodjournal.hematologylibrary.org/content/116/14/2608.full.pdf |
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Structures | ||
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) | |
Citation (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 |