title: MiRNA-Based Regulation of Hemostatic Factors through Hepatic Nuclear Factor-4 Alpha.
abstract: MiRNAs have been reported as CIS-acting elements of several hemostatic factors, however, their mechanism as TRANS-acting elements mediated by a transcription factor is little known and could have important effects. HNF4α has a direct and important role in the regulation of multiple hepatic coagulation genes. Previous in vitro studies have demonstrated that miR-24-3p and miR-34a-5p regulate HNF4A expression. Here we aimed to investigate the molecular mechanisms of miR-24 and miR-34a on coagulation through HNF4A. Transfections with miR-24 and miR-34a in HepG2 cells decreased not only HNF4A but also F10, F12, SERPINC1, PROS1, PROC, and PROZ transcripts levels. Positive and significant correlations were observed between levels of HNF4A and several hemostatic factors (F5, F8, F9, F11, F12, SERPINC1, PROC, and PROS1) in human liver samples (N = 104). However, miR-24 and miR-34a levels of the low (10th) and high (90th) percentiles of those liver samples were inversely correlated with HNF4A and almost all hemostatic factors expression levels. These outcomes suggest that miR-24 and miR-34a might be two indirect elements of regulation of several hemostatic factors. Additionally, variations in miRNA expression profiles could justify, at least in part, changes in HNF4A expression levels and its downstream targets of coagulation.
authors.affiliation: Centro Regional de Hemodonación, IMIB-Arrixaca, University of Murcia, Murcia, Spain.
authors.forename: Salam
authors.initials: S
authors.lastname: Salloum-Asfar
authors.affiliation: Centro Regional de Hemodonación, IMIB-Arrixaca, University of Murcia, Murcia, Spain.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Arroyo
authors.affiliation: Centro Regional de Hemodonación, IMIB-Arrixaca, University of Murcia, Murcia, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Teruel-Montoya
authors.affiliation: Centro Regional de Hemodonación, IMIB-Arrixaca, University of Murcia, Murcia, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: García-Barberá
authors.affiliation: Centro Regional de Hemodonación, IMIB-Arrixaca, University of Murcia, Murcia, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Roldán
authors.affiliation: Centro Regional de Hemodonación, IMIB-Arrixaca, University of Murcia, Murcia, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Vicente
authors.affiliation: Centro Regional de Hemodonación, IMIB-Arrixaca, University of Murcia, Murcia, Spain.
authors.forename: Constantino
authors.initials: C
authors.lastname: Martínez
authors.affiliation: Centro Regional de Hemodonación, IMIB-Arrixaca, University of Murcia, Murcia, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: González-Conejero
mesh_terms: D000990:Antithrombin III / Q000235:genetics / Q000378:metabolism; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D017293:Protein S
chemical_list: D001798:Blood Proteins; C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; C543845:MIRN24 microRNA, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; C523390:PROS1 protein, human; D017293:Protein S; C542513:SERPINC1 protein, human; C026080:plasma protein Z; D000990:Antithrombin III