MiR-203a is differentially expressed during branching morphogenesis and EMT in breast progenitor cells and is a repressor of peroxidasin

• Published in: Mechanisms of Development
• Main Authors: Briem, Eiríkur, Budkova, Zuzana, Sigurðardóttir, Anna Karen, Hilmarsdóttir, Bylgja, Kricker, Jennifer, Timp, Winston, Magnusson, Magnus Karl, Traustadottir, Gunnhildur Asta, Gudjonsson, Thorarinn
• Other Authors: Læknadeild (HÍ), Faculty of Medicine (UI), Lífvísindasetur (HÍ), Biomedical Center (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland
• Format: Article in Journal/Newspaper
• Language: English
• Published: Elsevier BV 2019
• Subjects: Developmental Biology; Embryology; MicroRNA; EMT; Þroskunarfræði; Fósturfræði; Genarannsóknir; Iceland
• Online Access: https://hdl.handle.net/20.500.11815/1818; https://doi.org/10.1016/j.mod.2018.11.002

Publisher's version MicroRNAs regulate developmental events such as branching morphogenesis, epithelial to mesenchymal transition (EMT) and its reverse process mesenchymal to epithelial transition (MET). In this study, we performed small RNA sequencing of a breast epithelial progenitor cell line (D492), and its mesenchymal derivative (D492M) cultured in three-dimensional microenvironment. Among the most downregulated miRNAs in D492M was miR-203a, a miRNA that plays an important role in epithelial differentiation. Increased expression of miR-203a was seen in D492, concomitant with increased complexity of branching. When miR-203a was overexpressed in D492M, a partial reversion towards epithelial phenotype was seen. Gene expression analysis of D492M and D492MmiR-203a revealed peroxidasin, a collagen IV cross-linker, as the most significantly downregulated gene in D492MmiR-203a. Collectively, we demonstrate that miR-203a expression temporally correlates with branching morphogenesis and is suppressed in D492M. Overexpression of miR-203a in D492M induces a partial MET and reduces the expression of peroxidasin. Furthermore, we demonstrate that miR-203a is a novel repressor of peroxidasin. MiR-203-peroxidasin axis may be an important regulator in branching morphogenesis, EMT/MET and basement membrane remodeling. This work was supported by Grants from Landspitali University Hospital Science Fund, University of Iceland Research Fund, and Icelandic Science and Technology Policy - Grant of Excellence: 152144051. ‘Göngum saman’, a supporting group for breast cancer research in Iceland (www.gongumsaman.is). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Primary cells were received from reduction mammoplasty after acquiring informed consent from the donor. Approved by the Icelandic National Bioethics Committee VSN-13-057. Peer Reviewed