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MicroRNA expression and gene regulation drive breast cancer progression and metastasis in PyMT mice

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNA molecules of about 22 nucleotides which function to silence the expression of their target genes. Numerous studies have shown that miRNAs are not only key regulators in important cellular processes but are also drivers in the development of man...

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Autores principales: Nogales-Cadenas, Ruben, Cai, Ying, Lin, Jhih-Rong, Zhang, Quanwei, Zhang, Wen, Montagna, Cristina, Zhang, Zhengdong D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4957901/
https://www.ncbi.nlm.nih.gov/pubmed/27449149
http://dx.doi.org/10.1186/s13058-016-0735-z
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author Nogales-Cadenas, Ruben
Cai, Ying
Lin, Jhih-Rong
Zhang, Quanwei
Zhang, Wen
Montagna, Cristina
Zhang, Zhengdong D.
author_facet Nogales-Cadenas, Ruben
Cai, Ying
Lin, Jhih-Rong
Zhang, Quanwei
Zhang, Wen
Montagna, Cristina
Zhang, Zhengdong D.
author_sort Nogales-Cadenas, Ruben
collection PubMed
description BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNA molecules of about 22 nucleotides which function to silence the expression of their target genes. Numerous studies have shown that miRNAs are not only key regulators in important cellular processes but are also drivers in the development of many diseases, especially cancer. Estrogen receptor positive luminal B is the second most common but the least studied subtype of breast cancer. Only a few studies have examined the expression profiles of miRNAs in luminal B breast cancer, and their regulatory roles in cancer progression have yet to be investigated. METHODS: In this study, using polyoma middle T antigen (PyMT) mice, a widely used luminal B breast cancer model, we profiled microRNA (miRNA) expression at four time points that represent different key developmental stages of cancer progression. We considered the expression of both miRNAs and messenger RNAs (mRNAs) at these time points to improve the identification of regulatory targets of miRNAs. By combining gene functional and pathway annotation with miRNA-mRNA interactions, we created a PyMT-specific tripartite miRNA-mRNA-pathway network and identified novel functional regulatory programs (FRPs). RESULTS: We identified 151 differentially expressed miRNAs with a strict dual nature of either upregulation or downregulation during the whole course of disease progression. Among 82 newly discovered breast-cancer-related miRNAs, 35 can potentially regulate 271 protein-coding genes based on their sequence complementarity and expression profiles. We also identified miRNA-mRNA regulatory modules driving specific cancer-related biological processes. CONCLUSIONS: In this study we profiled the expression of miRNAs during breast cancer progression in the PyMT mouse model. By integrating miRNA and mRNA expression profiles, we identified differentially expressed miRNAs and their target genes involved in several hallmarks of cancer. We applied a novel clustering method to an annotated miRNA-mRNA regulatory network and identified network modules involved in specific cancer-related biological processes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-016-0735-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-49579012016-07-23 MicroRNA expression and gene regulation drive breast cancer progression and metastasis in PyMT mice Nogales-Cadenas, Ruben Cai, Ying Lin, Jhih-Rong Zhang, Quanwei Zhang, Wen Montagna, Cristina Zhang, Zhengdong D. Breast Cancer Res Research Article BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNA molecules of about 22 nucleotides which function to silence the expression of their target genes. Numerous studies have shown that miRNAs are not only key regulators in important cellular processes but are also drivers in the development of many diseases, especially cancer. Estrogen receptor positive luminal B is the second most common but the least studied subtype of breast cancer. Only a few studies have examined the expression profiles of miRNAs in luminal B breast cancer, and their regulatory roles in cancer progression have yet to be investigated. METHODS: In this study, using polyoma middle T antigen (PyMT) mice, a widely used luminal B breast cancer model, we profiled microRNA (miRNA) expression at four time points that represent different key developmental stages of cancer progression. We considered the expression of both miRNAs and messenger RNAs (mRNAs) at these time points to improve the identification of regulatory targets of miRNAs. By combining gene functional and pathway annotation with miRNA-mRNA interactions, we created a PyMT-specific tripartite miRNA-mRNA-pathway network and identified novel functional regulatory programs (FRPs). RESULTS: We identified 151 differentially expressed miRNAs with a strict dual nature of either upregulation or downregulation during the whole course of disease progression. Among 82 newly discovered breast-cancer-related miRNAs, 35 can potentially regulate 271 protein-coding genes based on their sequence complementarity and expression profiles. We also identified miRNA-mRNA regulatory modules driving specific cancer-related biological processes. CONCLUSIONS: In this study we profiled the expression of miRNAs during breast cancer progression in the PyMT mouse model. By integrating miRNA and mRNA expression profiles, we identified differentially expressed miRNAs and their target genes involved in several hallmarks of cancer. We applied a novel clustering method to an annotated miRNA-mRNA regulatory network and identified network modules involved in specific cancer-related biological processes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-016-0735-z) contains supplementary material, which is available to authorized users. BioMed Central 2016-07-22 2016 /pmc/articles/PMC4957901/ /pubmed/27449149 http://dx.doi.org/10.1186/s13058-016-0735-z Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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.
spellingShingle Research Article
Nogales-Cadenas, Ruben
Cai, Ying
Lin, Jhih-Rong
Zhang, Quanwei
Zhang, Wen
Montagna, Cristina
Zhang, Zhengdong D.
MicroRNA expression and gene regulation drive breast cancer progression and metastasis in PyMT mice
title MicroRNA expression and gene regulation drive breast cancer progression and metastasis in PyMT mice
title_full MicroRNA expression and gene regulation drive breast cancer progression and metastasis in PyMT mice
title_fullStr MicroRNA expression and gene regulation drive breast cancer progression and metastasis in PyMT mice
title_full_unstemmed MicroRNA expression and gene regulation drive breast cancer progression and metastasis in PyMT mice
title_short MicroRNA expression and gene regulation drive breast cancer progression and metastasis in PyMT mice
title_sort microrna expression and gene regulation drive breast cancer progression and metastasis in pymt mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4957901/
https://www.ncbi.nlm.nih.gov/pubmed/27449149
http://dx.doi.org/10.1186/s13058-016-0735-z
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