Background: MicroRNAs (miRNAs) show differential expression across breast cancer subtypes and have both\noncogenic and tumor-suppressive roles. Numerous microarray studies reported different expression patterns of\nmiRNAs in breast cancers and found clinical interest for several miRNAs but often with contradictory results. Aim\nof this study is to identify miRNAs that are differentially expressed in estrogen receptor positive (ER+) and negative\n(ER?) breast primary tumors to better understand the molecular basis for the phenotypic differences between these\ntwo sub-types of carcinomas and to find potential clinically relevant miRNAs.\nMethods: We used the robust and reproductive tool of quantitative RT-PCR in a large cohort of well-annotated 153\nbreast cancers with long-term follow-up to identify miRNAs specifically differentially expressed between ER+ and ER?\nbreast cancers. Cytotoxicity tests and transfection experiments were then used to examine the role and the regulation\nmechanisms of selected miRNAs.\nResults: We identified a robust collection of 20 miRNAs significantly deregulated in ER+ compared to ER? breast\ncancers : 12 up-regulated and eight down-regulated miRNAs. MiR-190b retained our attention as it was the miRNA the\nmost strongly over-expressed in ER+ compared to ER? with a fold change upper to 23. It was also significantly upregulated\nin ER+/Normal breast tissue and down-regulated in ER?/Normal breast tissue. Functional experiments showed\nthat miR-190b expression is not directly regulated by estradiol and that miR-190b does not affect breast cancer cell lines\nproliferation. Expression level of miR-190b impacts metastasis-free and event-free survival independently of ER status.\nConclusions: This study reveals miR-190b as the highest up-regulated miRNA in hormone-dependent breast cancers.\nDue to its specificity and high expression level, miR-190b could therefore represent a new biomarker in hormonedependent\nbreast cancers but its exact role carcinogenesis remains to elucidate.
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