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A Novel Network Profiling Analysis Reveals System Changes in Epithelial-Mesenchymal Transition
Patient-specific analysis of molecular networks is a promising strategy for making individual risk predictions and treatment decisions in cancer therapy. Although systems biology allows the gene network of a cell to be reconstructed from clinical gene expression data, traditional methods, such as Ba...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110206/ https://www.ncbi.nlm.nih.gov/pubmed/21687740 http://dx.doi.org/10.1371/journal.pone.0020804 |
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author | Shimamura, Teppei Imoto, Seiya Shimada, Yukako Hosono, Yasuyuki Niida, Atsushi Nagasaki, Masao Yamaguchi, Rui Takahashi, Takashi Miyano, Satoru |
author_facet | Shimamura, Teppei Imoto, Seiya Shimada, Yukako Hosono, Yasuyuki Niida, Atsushi Nagasaki, Masao Yamaguchi, Rui Takahashi, Takashi Miyano, Satoru |
author_sort | Shimamura, Teppei |
collection | PubMed |
description | Patient-specific analysis of molecular networks is a promising strategy for making individual risk predictions and treatment decisions in cancer therapy. Although systems biology allows the gene network of a cell to be reconstructed from clinical gene expression data, traditional methods, such as Bayesian networks, only provide an averaged network for all samples. Therefore, these methods cannot reveal patient-specific differences in molecular networks during cancer progression. In this study, we developed a novel statistical method called NetworkProfiler, which infers patient-specific gene regulatory networks for a specific clinical characteristic, such as cancer progression, from gene expression data of cancer patients. We applied NetworkProfiler to microarray gene expression data from 762 cancer cell lines and extracted the system changes that were related to the epithelial-mesenchymal transition (EMT). Out of 1732 possible regulators of E-cadherin, a cell adhesion molecule that modulates the EMT, NetworkProfiler, identified 25 candidate regulators, of which about half have been experimentally verified in the literature. In addition, we used NetworkProfiler to predict EMT-dependent master regulators that enhanced cell adhesion, migration, invasion, and metastasis. In order to further evaluate the performance of NetworkProfiler, we selected Krueppel-like factor 5 (KLF5) from a list of the remaining candidate regulators of E-cadherin and conducted in vitro validation experiments. As a result, we found that knockdown of KLF5 by siRNA significantly decreased E-cadherin expression and induced morphological changes characteristic of EMT. In addition, in vitro experiments of a novel candidate EMT-related microRNA, miR-100, confirmed the involvement of miR-100 in several EMT-related aspects, which was consistent with the predictions obtained by NetworkProfiler. |
format | Online Article Text |
id | pubmed-3110206 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31102062011-06-16 A Novel Network Profiling Analysis Reveals System Changes in Epithelial-Mesenchymal Transition Shimamura, Teppei Imoto, Seiya Shimada, Yukako Hosono, Yasuyuki Niida, Atsushi Nagasaki, Masao Yamaguchi, Rui Takahashi, Takashi Miyano, Satoru PLoS One Research Article Patient-specific analysis of molecular networks is a promising strategy for making individual risk predictions and treatment decisions in cancer therapy. Although systems biology allows the gene network of a cell to be reconstructed from clinical gene expression data, traditional methods, such as Bayesian networks, only provide an averaged network for all samples. Therefore, these methods cannot reveal patient-specific differences in molecular networks during cancer progression. In this study, we developed a novel statistical method called NetworkProfiler, which infers patient-specific gene regulatory networks for a specific clinical characteristic, such as cancer progression, from gene expression data of cancer patients. We applied NetworkProfiler to microarray gene expression data from 762 cancer cell lines and extracted the system changes that were related to the epithelial-mesenchymal transition (EMT). Out of 1732 possible regulators of E-cadherin, a cell adhesion molecule that modulates the EMT, NetworkProfiler, identified 25 candidate regulators, of which about half have been experimentally verified in the literature. In addition, we used NetworkProfiler to predict EMT-dependent master regulators that enhanced cell adhesion, migration, invasion, and metastasis. In order to further evaluate the performance of NetworkProfiler, we selected Krueppel-like factor 5 (KLF5) from a list of the remaining candidate regulators of E-cadherin and conducted in vitro validation experiments. As a result, we found that knockdown of KLF5 by siRNA significantly decreased E-cadherin expression and induced morphological changes characteristic of EMT. In addition, in vitro experiments of a novel candidate EMT-related microRNA, miR-100, confirmed the involvement of miR-100 in several EMT-related aspects, which was consistent with the predictions obtained by NetworkProfiler. Public Library of Science 2011-06-07 /pmc/articles/PMC3110206/ /pubmed/21687740 http://dx.doi.org/10.1371/journal.pone.0020804 Text en Shimamura et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Shimamura, Teppei Imoto, Seiya Shimada, Yukako Hosono, Yasuyuki Niida, Atsushi Nagasaki, Masao Yamaguchi, Rui Takahashi, Takashi Miyano, Satoru A Novel Network Profiling Analysis Reveals System Changes in Epithelial-Mesenchymal Transition |
title | A Novel Network Profiling Analysis Reveals System Changes in Epithelial-Mesenchymal Transition |
title_full | A Novel Network Profiling Analysis Reveals System Changes in Epithelial-Mesenchymal Transition |
title_fullStr | A Novel Network Profiling Analysis Reveals System Changes in Epithelial-Mesenchymal Transition |
title_full_unstemmed | A Novel Network Profiling Analysis Reveals System Changes in Epithelial-Mesenchymal Transition |
title_short | A Novel Network Profiling Analysis Reveals System Changes in Epithelial-Mesenchymal Transition |
title_sort | novel network profiling analysis reveals system changes in epithelial-mesenchymal transition |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110206/ https://www.ncbi.nlm.nih.gov/pubmed/21687740 http://dx.doi.org/10.1371/journal.pone.0020804 |
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