MiRNA-Based Regulation of Hemostatic Factors through Hepatic Nuclear Factor-4 Alpha

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 coagulati...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2016-05, Vol.11 (5), p.e0154751
Main Authors: Salloum-Asfar, Salam, Arroyo, Ana B, Teruel-Montoya, Raúl, García-Barberá, Nuria, Roldán, Vanessa, Vicente, Vicente, Martínez, Constantino, González-Conejero, Rocío
Format: Article
Language:English
Subjects:
Antithrombin III - genetics
Antithrombin III - metabolism
Biology and Life Sciences
Blood Proteins - genetics
Blood Proteins - metabolism
Cell cycle
Coagulation
Gene expression
Hemostatic agents
Hep G2 Cells
Hepatocyte nuclear factor 4
Hepatocyte Nuclear Factor 4 - genetics
Hepatocyte Nuclear Factor 4 - metabolism
Humans
Liver
Liver - metabolism
Medicine and Health Sciences
MicroRNA
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
miRNA
Molecular modelling
People and Places
Physiology
Protein S
Proteins
Research and Analysis Methods
Rodents
Transcription (Genetics)
Transcription factors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0154751