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Cellular Oncology
Published in: Cellular Oncology 6/2015

Open Access 01-12-2015 | Original Paper

Identification of miR-10b, miR-26a, miR-146a and miR-153 as potential triple-negative breast cancer biomarkers

Authors: Insaf Fkih M’hamed, Maud Privat, Flora Ponelle, Frédérique Penault-Llorca, Abderraouf Kenani, Yves-Jean Bignon

Published in: Cellular Oncology | Issue 6/2015

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Abstract

Background

Familial triple-negative breast cancers are often linked to mutations in the BRCA1 tumor suppressor gene. In sporadic triple-negative breast cancers BRCA1 is frequently inactivated at the transcriptional level, and it has been reported that this inactivation may be brought about by promoter methylation. More recently, it was found that BRCA1 may also be regulated at the post-transcriptional level by miRNAs. Here, we explored the expression of putative BRCA1-regulating miRNAs in sporadic human triple-negative breast cancer cells.

Methods

Nine sporadic human breast cancer-derived cell lines and one benign breast epithelium-derived cell line were assessed for their hormone receptor, growth factor receptor and cytokeratin status by immunocytochemistry. The expression of 5 selected miRNAs predicted to target BRCA1 was assessed using qRT-PCR in the 10 cell lines. In addition, expression profiles of 84 known breast cancer-associated miRNAs were established in these 10 cell lines using PCR Array and qRT-PCR, respectively. The putative role of pre-selected candidate miRNAs in breast cancer development was assessed through exogenous expression of these miRNAs and their anti-miRNAs (‘antagomirs’) in MDA-MB-231 and MCF7 breast cancer-derived cells.

Results

Based on our expression profiling results, four candidate miRNAs (miR-10b, miR-26a, miR-146a and miR-153) were selected as being potentially involved in triple-negative breast cancer development. Exogenous expression assays revealed that miR-10b and miR-26a, but not miR-146a, can down-regulate the expression of BRCA1 in both triple-negative MDA-MB-231 and luminal epithelial MCF7 breast cancer-derived cells, whereas miR-153 could down-regulate BRCA1 expression only in MCF7 cells. In silico analysis of The Cancer Genome Atlas (TCGA) data confirmed that miR-146a is significantly higher expressed in triple-negative breast tumors compared to other (non triple-negative) breast tumors.

Conclusion

Our work provides evidence for the involvement of specific miRNAs in triple-negative breast cancer development through regulating BRCA1 expression.
Appendix
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Metadata
Title
Identification of miR-10b, miR-26a, miR-146a and miR-153 as potential triple-negative breast cancer biomarkers
Authors
Insaf Fkih M’hamed
Maud Privat
Flora Ponelle
Frédérique Penault-Llorca
Abderraouf Kenani
Yves-Jean Bignon
Publication date
01-12-2015
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 6/2015
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-015-0239-3

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