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PMID:25379760

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Citation

Salloum-Asfar, S, Teruel-Montoya, R, Arroyo, AB, García-Barberá, N, Chaudhry, A, Schuetz, E, Luengo-Gil, G, Vicente, V, González-Conejero, R and Martínez, C (2014) Regulation of Coagulation Factor XI Expression by MicroRNAs in the Human Liver. PLoS ONE 9:e111713

Abstract

High levels of factor XI (FXI) increase the risk of thromboembolic disease. However, the genetic and environmental factors regulating FXI expression are still largely unknown. The aim of our study was to evaluate the regulation of FXI by microRNAs (miRNAs) in the human liver. In silico prediction yielded four miRNA candidates that might regulate FXI expression. HepG2 cells were transfected with miR-181a-5p, miR-23a-3p, miR-16-5p and miR-195-5p. We used mir-494, which was not predicted to bind to F11, as a negative control. Only miR-181a-5p caused a significant decrease both in FXI protein and F11 mRNA levels. In addition, transfection with a miR-181a-5p inhibitor in PLC/PRF/5 hepatic cells increased both the levels of F11 mRNA and extracellular FXI. Luciferase assays in human colon cancer cells deficient for Dicer (HCT-DK) demonstrated a direct interaction between miR-181a-5p and 3'untranslated region of F11. Additionally, F11 mRNA levels were inversely and significantly correlated with miR-181a-5p levels in 114 healthy livers, but not with miR-494. This study demonstrates that FXI expression is directly regulated by a specific miRNA, miR-181a-5p, in the human liver. Future studies are necessary to further investigate the potential consequences of miRNA dysregulation in pathologies involving FXI.

Links

PubMed PMC4224396 Online version:10.1371/journal.pone.0111713

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:FA11

GO:0050818: regulation of coagulation

ECO:0000316:

UniProtKB:P03951


P

Figure 2 Effect of miRNAs on FXI expression

complete
CACAO 10392

Notes

See also

References

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