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- Title
Regulation of Coagulation Factor XI Expression by MicroRNAs in the Human Liver.
- Authors
Salloum-Asfar, Salam; Teruel-Montoya, Raúl; Arroyo, Ana B.; García-Barberá, Nuria; Chaudhry, Amarjit; Schuetz, Erin; Luengo-Gil, Ginés; Vicente, Vicente; González-Conejero, Rocío; Martínez, Constantino
- 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.
- Subjects
MICRORNA genetics; GENE expression; THROMBOEMBOLISM risk factors; GENOTYPE-environment interaction; LIVER cells; CANCER cells
- Publication
PLoS ONE, 2014, Vol 9, Issue 11, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0111713