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Breast Cancer Research
Published in: Breast Cancer Research 1/2016

Open Access 01-12-2016 | Research article

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

Authors: Ruben Nogales-Cadenas, Ying Cai, Jhih-Rong Lin, Quanwei Zhang, Wen Zhang, Cristina Montagna, Zhengdong D. Zhang

Published in: Breast Cancer Research | Issue 1/2016

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Abstract

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.
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Metadata
Title
MicroRNA expression and gene regulation drive breast cancer progression and metastasis in PyMT mice
Authors
Ruben Nogales-Cadenas
Ying Cai
Jhih-Rong Lin
Quanwei Zhang
Wen Zhang
Cristina Montagna
Zhengdong D. Zhang
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2016
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-016-0735-z

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