Integrated microRNA–mRNA profiling identifies oncostatinm as a marker of mesenchymal-like ER-negative/HER2-negative breast cancer

Giulia Bottai, Lixia Diao, Keith A. Baggerly, Laura Paladini, Balázs Győrffy, Carlotta Raschioni, Lajos Pusztai, George A. Calin, Libero Santarpia

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Article number194
JournalInternational Journal of Molecular Sciences
Volume18
Issue number1
DOIs
Publication statusPublished - Jan 19 2017

Fingerprint

estrogens
MicroRNAs
breast
Estrogen Receptors
markers
ribonucleic acids
cancer
Breast Neoplasms
Gene expression
Oncostatin M
Epithelial-Mesenchymal Transition
Cells
gene expression
Deregulation
Tumors
Dynamical systems
Messenger RNA
Genes
Tissue
profiles

Keywords

  • Breast cancer
  • Immune response
  • MicroRNAs
  • Molecular subtypes
  • Oncostatin M

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Integrated microRNA–mRNA profiling identifies oncostatinm as a marker of mesenchymal-like ER-negative/HER2-negative breast cancer. / Bottai, Giulia; Diao, Lixia; Baggerly, Keith A.; Paladini, Laura; Győrffy, Balázs; Raschioni, Carlotta; Pusztai, Lajos; Calin, George A.; Santarpia, Libero.

In: International Journal of Molecular Sciences, Vol. 18, No. 1, 194, 19.01.2017.

Research output: Contribution to journalArticle

@article{24fce08231ac48ffbbfa2701f0834953,
title = "Integrated microRNA–mRNA profiling identifies oncostatinm as a marker of mesenchymal-like ER-negative/HER2-negative breast cancer",
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.",
keywords = "Breast cancer, Immune response, MicroRNAs, Molecular subtypes, Oncostatin M",
author = "Giulia Bottai and Lixia Diao and Baggerly, {Keith A.} and Laura Paladini and Bal{\'a}zs Győrffy and Carlotta Raschioni and Lajos Pusztai and Calin, {George A.} and Libero Santarpia",
year = "2017",
month = "1",
day = "19",
doi = "10.3390/ijms18010194",
language = "English",
volume = "18",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "MDPI AG",
number = "1",

}

TY - JOUR

T1 - Integrated microRNA–mRNA profiling identifies oncostatinm as a marker of mesenchymal-like ER-negative/HER2-negative breast cancer

AU - Bottai, Giulia

AU - Diao, Lixia

AU - Baggerly, Keith A.

AU - Paladini, Laura

AU - Győrffy, Balázs

AU - Raschioni, Carlotta

AU - Pusztai, Lajos

AU - Calin, George A.

AU - Santarpia, Libero

PY - 2017/1/19

Y1 - 2017/1/19

N2 - 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.

AB - 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.

KW - Breast cancer

KW - Immune response

KW - MicroRNAs

KW - Molecular subtypes

KW - Oncostatin M

UR - http://www.scopus.com/inward/record.url?scp=85010782677&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85010782677&partnerID=8YFLogxK

U2 - 10.3390/ijms18010194

DO - 10.3390/ijms18010194

M3 - Article

VL - 18

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 1

M1 - 194

ER -