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Int. J. Mol. Sci. 2017, 18(1), 194; doi:10.3390/ijms18010194

Integrated MicroRNA–mRNA Profiling Identifies Oncostatin M as a Marker of Mesenchymal-Like ER-Negative/HER2-Negative Breast Cancer

1
Oncology Experimental Therapeutics, Humanitas Clinical and Research Institute, 20089 Rozzano-Milan, Italy
2
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
3
2nd Department of Pediatrics, Semmelweis University, H-1094 Budapest, Hungary
4
MTA TTK Lendület Cancer Biomarker Research Group, Hungarian Academy of Sciences, H-1117 Budapest, Hungary
5
Department of Breast Medical Oncology, Yale University, Yale Cancer Center, New Haven, CT 06520, USA
6
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
7
RNA Interference and Non-Coding RNA Center, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Nicoletta Sacchi
Received: 8 December 2016 / Revised: 12 January 2017 / Accepted: 13 January 2017 / Published: 19 January 2017
(This article belongs to the Special Issue Cancer Epigenetics)
View Full-Text   |   Download PDF [2166 KB, uploaded 19 January 2017]   |  

Abstract

MicroRNAs (miRNAs) simultaneously modulate different oncogenic networks, establishing a dynamic system of gene expression and pathway regulation. In this study, we analyzed global miRNA and messenger RNA (mRNA) expression profiles of 17 cell lines representing different molecular breast cancer subtypes. Spearman’s rank correlation test was used to evaluate the correlation between miRNA and mRNA expression. Hierarchical clustering and pathway analysis were also performed. Publicly available gene expression profiles (n = 699) and tumor tissues (n = 80) were analyzed to assess the relevance of key miRNA-regulated pathways in human breast cancer. We identified 39 significantly deregulated miRNAs, and the integration between miRNA and mRNA data revealed the importance of immune-related pathways, particularly the Oncostatin M (OSM) signaling, associated with mesenchymal-like breast cancer cells. OSM levels correlated with genes involved in the inflammatory response, epithelial-to-mesenchymal transition (EMT), and epidermal growth factor (EGF) signaling in human estrogen receptor (ER)-negative/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Our results suggest that the deregulation of specific miRNAs may cooperatively impair immune and EMT pathways. The identification of the OSM inflammatory pathway as an important mediator of EMT in triple-negative breast cancer (TNBC) may provide a novel potential opportunity to improve therapeutic strategies. View Full-Text
Keywords: breast cancer; microRNAs; molecular subtypes; immune response; Oncostatin M breast cancer; microRNAs; molecular subtypes; immune response; Oncostatin M
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Bottai, G.; Diao, L.; Baggerly, K.A.; Paladini, L.; Győrffy, B.; Raschioni, C.; Pusztai, L.; Calin, G.A.; Santarpia, L. Integrated MicroRNA–mRNA Profiling Identifies Oncostatin M as a Marker of Mesenchymal-Like ER-Negative/HER2-Negative Breast Cancer. Int. J. Mol. Sci. 2017, 18, 194.

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