A global microRNA screen identifies regulators of the ErbB receptor signaling network

Cell Communication and Signaling

Research

Michaela Bayerlová¹  Tim Beissbarth¹  Monilola A Olayioye²  Annabell Bischoff²  Simone Schmid²  Michaela Strotbek² 

[1] Department of Medical Statistics, University Medical Center Göttingen, 37099, Göttingen, Germany;Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany;

关键词: MicroRNA/miRNA;    ErbB3/HER3;    Heregulin;    PI3K-Akt pathway;    Breast cancer;   

DOI  :  10.1186/s12964-015-0084-z

 received in 2014-06-12, accepted in 2015-01-12,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThe growth factor heregulin (HRG) potently stimulates epithelial cell survival and proliferation through the binding of its cognate receptor ErbB3 (also known as HER3). ErbB3-dependent signal transmission relies on the dimerization partner ErbB2, a receptor tyrosine kinase that is frequently overexpressed and/or amplified in breast cancer cells. Substantial evidence suggests that deregulated ErbB3 expression also contributes to the transformed phenotype of breast cancer cells.ResultsBy genome-wide screening, we identify 43 microRNAs (miRNAs) that specifically impact HRG-induced activation of the PI3K-Akt pathway. Bioinformatic analysis combined with experimental validation reveals a highly connected molecular miRNA-gene interaction network particularly for the negative screen hits. For selected miRNAs, namely miR-149, miR-148b, miR-326, and miR-520a-3p, we demonstrate the simultaneous downregulation of the ErbB3 receptor and multiple downstream signaling molecules, explaining their efficient dampening of HRG responses and ascribing to these miRNAs potential context-dependent tumor suppressive functions.ConclusionsGiven the contribution of HRG signaling and the PI3K-Akt pathway in particular to tumorigenesis, this study not only provides mechanistic insight into the function of miRNAs but also has implications for future clinical applications.

【 授权许可】

Unknown   
© Bischoff et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.