title: MicroRNA-132 targets HB-EGF upon IgE-mediated activation in murine and human mast cells.
abstract: MicroRNAs provide an additional layer in the regulation of gene expression acting as repressors with several targets at the posttranscriptional level. This study describes microRNA expression patterns during differentiation and activation of mast cells. The expression levels of 567 different mouse miRNAs were compared by microarray between c-Kit+ committed progenitors, mucosal mast cells, resting and IgE-crosslinked BMMCs in vitro. The strongest upregulation of miR-132 upon IgE-mediated activation was validated in human cord blood-derived mast cells as well. HB-EGF growth factor also upregulated upon activation and was ranked high by more prediction algorithms. Co-transfection of miR-132 mimicking precursor and the 3'UTR of human Hbegf-containing luciferase vector proves that the predicted binding site is functional. In line with this, neutralization of miR-132 by anti-miR inhibitor leads to sustained production of HB-EGF protein in activated mast cells. Our data provide a novel example for negative regulation of a growth factor by an upregulated miRNA.
authors.affiliation: Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary. molvik.dgci@gmail.com
authors.forename: Viktor
authors.initials: V
authors.lastname: Molnár
authors.forename: Barbara
authors.initials: B
authors.lastname: Érsek
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Wiener
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Tömböl
authors.forename: Péter M
authors.initials: PM
authors.lastname: Szabó
authors.forename: Péter
authors.initials: P
authors.lastname: Igaz
authors.forename: András
authors.initials: A
authors.lastname: Falus
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D005312:Fetal Blood / Q000166:cytology; D020869:Gene Expression Profiling; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; C547077:MIRN132 microRNA, human; D035683:MicroRNAs; D007073:Immunoglobulin E