Open AccessRegulation of Coagulation Factor XI Expression by MicroRNAs in the Human Liver
Author(s) -
Salam Salloum-Asfar,
Raúl TeruelMontoya,
Ana B. Arroyo,
Nuria GarcíaBarbera,
Amarjit S. Chaudhry,
Erin G. Schuetz,
Ginés LuengoGil,
Vicente Vicente,
Rocı́o González-Conejero,
Constantino Martı́nez
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0111713
Subject(s) - microrna , transfection , biology , tissue factor , luciferase , in silico , messenger rna , regulation of gene expression , three prime untranslated region , microbiology and biotechnology , untranslated region , coagulation , gene , medicine , genetics
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.