title: Global microRNA expression profiling identifies MiR-210 associated with tumor proliferation, invasion and poor clinical outcome in breast cancer.
abstract: OBJECTIVE
  Aberrant microRNA (miRNA) expression is associated with cancer and has potential diagnostic and prognostic value in various malignancies. In this study, we investigated miRNA profiling as a complementary tool to improve our understanding of breast cancer (BC) biology and to assess whether miRNA expression could predict clinical outcome of BC patients.
  
  
  METHODS
  Global miRNA expression profiling using microarray technology was conducted in 56 systemically untreated BC patients who had corresponding mRNA expression profiles available. Results were further confirmed using qRT-PCR in an independent dataset of 89 ER-positive BC patients homogeneously treated with tamoxifen only. MiR-210 functional analyses were performed in MCF7 and MDA-MB-231 BC cell lines using lentiviral transduction.
  
  
  RESULTS
  Estrogen receptor (ER) status, tumor grade and our previously developed gene expression grade index (GGI) were associated with distinct miRNA profiles. Several miRNAs were found to be clinically relevant, including miR-210, its expression being associated with tumor proliferation and differentiation. Furthermore, miR-210 was associated with poor clinical outcome in ER-positive, tamoxifen-treated BC patients. Interestingly, the prognostic performance of miR-210 was similar to several reported multi-gene signatures, highlighting its important role in BC differentiation and tumor progression. Functional analyses in BC cell lines revealed that miR-210 is involved in cell proliferation, migration and invasion.
  
  
  CONCLUSIONS
  This integrated analysis combining miRNA and mRNA expression demonstrates that miRNA expression provides additional biological information beyond mRNA expression. Expression of miR-210 is linked to tumor proliferation and appears to be a strong potential biomarker of clinical outcome in BC.
authors: Translational Research Unit, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium.
authors: Françoise
authors: F
authors: Rothé
authors: Michail
authors: M
authors: Ignatiadis
authors: Carole
authors: C
authors: Chaboteaux
authors: Benjamin
authors: B
authors: Haibe-Kains
authors: Naïma
authors: N
authors: Kheddoumi
authors: Samira
authors: S
authors: Majjaj
authors: Bassam
authors: B
authors: Badran
authors: Hussein
authors: H
authors: Fayyad-Kazan
authors: Christine
authors: C
authors: Desmedt
authors: Adrian L
authors: AL
authors: Harris
authors: Martine
authors: M
authors: Piccart
authors: Christos
authors: C
authors: Sotiriou
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D013629:Tamoxifen / Q000627:therapeutic use
chemical_list: D035683:MicroRNAs; D013629:Tamoxifen