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PMID:25379760
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 |
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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 |
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Significance
Annotations
Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
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GO:0050818: regulation of coagulation |
ECO:0000316: |
UniProtKB:P03951
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P |
Figure 2 Effect of miRNAs on FXI expression |
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Notes
See also
References
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