miR-139-5p is a regulator of metastatic pathways in breast cancer

Krishnan, Keerthana, Steptoe, Anita, Martin, Hilary, Pattabiraman, Diwakar R., Nones, Katia, Waddell, Nicola, Mariasegaram, Mythily, Simpson, Peter T., Lakhani, Sunil R., Vlassov, Alexander, Grimmond, Sean M. and Cloonan, Nicole (2013) miR-139-5p is a regulator of metastatic pathways in breast cancer. RNA, 19 12: 1767-1780. doi:10.1261/rna.042143.113

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Author Krishnan, Keerthana
Steptoe, Anita
Martin, Hilary
Pattabiraman, Diwakar R.
Nones, Katia
Waddell, Nicola
Mariasegaram, Mythily
Simpson, Peter T.
Lakhani, Sunil R.
Vlassov, Alexander
Grimmond, Sean M.
Cloonan, Nicole
Title miR-139-5p is a regulator of metastatic pathways in breast cancer
Journal name RNA   Check publisher's open access policy
ISSN 1355-8382
Publication date 2013-12-01
Year available 2013
Sub-type Article (original research)
DOI 10.1261/rna.042143.113
Open Access Status File (Publisher version)
Volume 19
Issue 12
Start page 1767
End page 1780
Total pages 14
Place of publication Woodbury, NY, United States
Publisher Cold Spring Harbor Laboratory Press
Language eng
Abstract Metastasis is a complex, multistep process involved in the progression of cancer from a localized primary tissue to distant sites, often characteristic of the more aggressive forms of this disease. Despite being studied in great detail in recent years, the mechanisms that govern this process remain poorly understood. In this study, we identify a novel role for miR-139-5p in the inhibition of breast cancer progression. We highlight its clinical relevance by reviewing miR-139-5p expression across a wide variety of breast cancer subtypes using in-house generated and online data sets to show that it is most frequently lost in invasive tumors. A biotin pull-down approach was then used to identify the mRNA targets of miR-139-5p in the breast cancer cell line MCF7. Functional enrichment analysis of the pulled-down targets showed significant enrichment of genes in pathways previously implicated in breast cancer metastasis (P < 0.05). Further bioinformatic analysis revealed a predicted disruption to the TGFβ, Wnt, Rho, and MAPK/PI3K signaling cascades, implying a potential role for miR-139-5p in regulating the ability of cells to invade and migrate. To corroborate this finding, using the MDA-MB-231 breast cancer cell line, we show that overexpression of miR-139-5p results in suppression of these cellular phenotypes. Furthermore, we validate the interaction between miR-139-5p and predicted targets involved in these pathways. Collectively, these results suggest a significant functional role for miR-139-5p in breast cancer cell motility and invasion and its potential to be used as a prognostic marker for the aggressive forms of breast cancer.
Keyword Biomarker
Breast cancer
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID DP1093164
Institutional Status UQ

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Created: Fri, 22 Nov 2013, 19:42:14 EST by Susan Allen on behalf of Institute for Molecular Bioscience