title: Identification of miR-10b, miR-26a, miR-146a and miR-153 as potential triple-negative breast cancer biomarkers.
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.
  
  
  CONCLUSIONS
  Our work provides evidence for the involvement of specific miRNAs in triple-negative breast cancer development through regulating BRCA1 expression.
authors.affiliation: Département d'Oncogénétique, Centre Jean Perrin, BP 392, 63011, Clermont-Ferrand, France.|EA4677 ERTICA, Université d'Auvergne, Clermont-Ferrand, France.|Faculté de médecine de Monastir, Laboratoire de Biochimie, Unité de recherche UR 12ES08 "Signalisation Cellulaire et Pathologies", 5019, Monastir, Tunisie.
authors.forename: Insaf
authors.initials: I
authors.lastname: Fkih M'hamed
authors.affiliation: Département d'Oncogénétique, Centre Jean Perrin, BP 392, 63011, Clermont-Ferrand, France.|EA4677 ERTICA, Université d'Auvergne, Clermont-Ferrand, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Privat
authors.affiliation: Département d'Oncogénétique, Centre Jean Perrin, BP 392, 63011, Clermont-Ferrand, France.|EA4677 ERTICA, Université d'Auvergne, Clermont-Ferrand, France.
authors.forename: Flora
authors.initials: F
authors.lastname: Ponelle
authors.affiliation: EA4677 ERTICA, Université d'Auvergne, Clermont-Ferrand, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Penault-Llorca
authors.affiliation: Faculté de médecine de Monastir, Laboratoire de Biochimie, Unité de recherche UR 12ES08 "Signalisation Cellulaire et Pathologies", 5019, Monastir, Tunisie.
authors.forename: Abderraouf
authors.initials: A
authors.lastname: Kenani
authors.affiliation: Département d'Oncogénétique, Centre Jean Perrin, BP 392, 63011, Clermont-Ferrand, France. Yves-Jean.Bignon@cjp.fr.|EA4677 ERTICA, Université d'Auvergne, Clermont-Ferrand, France. Yves-Jean.Bignon@cjp.fr.
authors.forename: Yves-Jean
authors.initials: YJ
authors.lastname: Bignon
mesh_terms: D000465:Algorithms; D019313:BRCA1 Protein / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000032:analysis / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D059467:Transcriptome; D014162:Transfection; D064726:Triple Negative Breast Neoplasms / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; D014408:Biomarkers, Tumor; D035683:MicroRNAs; C492913:BRCA1 protein, human; C547183:MIRN10 microRNA, human; C542542:MIRN146 microRNA, human; C556500:MIRN153 microRNA, human; C528163:MIRN26 microRNA, human
keywords: BRCA1; Human triple-negative breast cancer cells; MicroRNAs; Regulation