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Scientific article
English

Regulation of fibrinogen production by microRNAs

Published inBlood, vol. 116, no. 14, p. 2608-2615
Publication date2010
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
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
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ISSN of the journal0006-4971
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