Abstract
PurposeAberrant 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.Experimental DesignGlobal 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.ResultsEstrogen 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.ConclusionsThis 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.
Highlights
MicroRNAs are evolutionary conserved, small noncoding RNA molecules that negatively regulate gene expression
Expression of miR-210 is linked to tumor proliferation and appears to be a strong potential biomarker of clinical outcome in breast cancer (BC)
MiRNA expression profiles from human breast tumors MiRNA expression profiles were generated from 73 BC freshfrozen samples with available mRNA profiling expression data using an optimized microarray platform for miRNA profiling
Summary
MicroRNAs (miRNAs) are evolutionary conserved, small noncoding RNA molecules that negatively regulate gene expression. Recent studies have demonstrated that mutations in miRNAs or their aberrant expression are associated with diverse human diseases, including cancers, suggesting that miRNAs may act as oncogenes or tumor suppressor genes. MiRNA genes are frequently located at fragile sites and cancer-associated genomic regions. MiRNA expression signatures have emerged from several studies. Recent findings have linked deregulated miRNA expression to tumor metastasis in breast cancer (BC) cells [4,5]. These results suggest that aberrant miRNA expression may be important for the pathogenesis of this malignancy. Several miRNAs were reported to be associated with the clinical outcome of patients with chronic lymphocytic leukaemia [6], lung [7,8] and ovarian cancers [9]
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