Global MicroRNA Expression Profiling Identifies MiR-210 Associated with Tumor Proliferation, Invasion and Poor Clinical Outcome in Breast Cancer

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.

A Systematic Approach to Defining the microRNA Landscape in Metastasis

“…Interestingly, miR-135b targets members of the Hippo pathway that has been associated with determining stemness-like properties (34), which is likely to be relevant to the role of miR-135b in cancer progression. Mechanistic studies on miR-210 have focused on a putative function in hypoxia-associated processes, and a few metastasis-relevant targets of miR-210 have been characterized (35). By demonstrating the targeting of the tumor suppressors SIAH1 and SETD2 and the little studied FOXN3 transcription factor, the findings we report here substantially advance our knowledge about the function of miR-135b and miR-210.…”

Direct Comparison of Metastasis-Related miRNAs Expression Levels in Circulating Tumor Cells, Corresponding Plasma, and Primary Tumors of Breast Cancer Patients

“…The selection of these miRNAs was based on their critical role in the multistep metastatic process. Indeed, miR-21 is involved in invasion (31 ), miR-146a in invasion and migration (32 ), miR-210 in tumor proliferation and hypoxia (33,34 ), and miR-200c in mesenchymal-toepithelial transition (35 ).…”

MicroRNAs and cancer: Key paradigms in molecular therapy (Review)

“…In breast cancer, 31 miRNAs were demonstrated to be significantly associated with clinical factors, while the overexpression of 17 miRNAs was associated with estrogen-receptor-positive stage I or II breast cancer, with good clinical outcome (63). The overexpression of miR-210 is associated with an increased risk of recurrence and a reduced chance of relapse-free survival (64). miR-155 overexpression exhibits an association with poor post-operative survival in lung cancer and B cell lymphomas (65,66).…”