title: miR-421 and miR-30c inhibit SERPINE 1 gene expression in human endothelial cells.
abstract: In this work, we assessed whether SERPINE1 expression could be under the influence of microRNAs (miRNAs) predicted to bind the SERPINE1 3'UTR region. We specifically focused on the 3'UTR region harboring a common polymorphism, rs1050955, that have been found associated to SERPINE1 monocyte expression, and investigated whether the presence of different alleles at rs1050955 could modify the miRNAs binding efficiency and affect PAI-1 protein levels. We demonstrated that, in human umbilical vein endothelial cells, both miR-421 and miR-30c directly interacted with PAI-1 mRNA to inhibit the expression of the associated protein. However, these inhibitory mechanisms were independent on the allele present at the rs1050955 locus. We further showed that miR-421 levels correlated with PAI-1 activity in the plasma sample of 40 patients with venous thrombosis. Our results strongly suggest that the regulation of PAI-1 molecule could be under the influence of several miRNAs whose measurement in the plasma of patients could be envisaged as a biomarker for inflammatory and thrombotic disorders.
authors.affiliation: UMR_S 956, INSERM, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Marchand
authors.forename: Carole
authors.initials: C
authors.lastname: Proust
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Morange
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Lompré
authors.forename: David-Alexandre
authors.initials: DA
authors.lastname: Trégouët
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D035683:MicroRNAs / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020246:Venous Thrombosis / Q000097:blood / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C546086:MIRN30b microRNA, human; C547665:MIRN421 microRNA, human; D035683:MicroRNAs; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C051321:SERPINE1 protein, human; D008156:Luciferases