miRNome Profiling Reveals Shared Features in Breast Cancer Subtypes and Highlights miRNAs That Potentially Regulate MYB and EZH2 Expression

Abstract

Breast cancer (BC) has been extensively studied, as it is one of the more commonly diagnosed cancer types worldwide. The study of miRNAs has increased what is known about the complexity of pathways and signaling and has identified potential biomarkers and therapeutic targets. Thus, miRNome profiling could provide important information regarding the molecular mechanisms involved in BC. On average, more than 430 miRNAs were identified as differentially expressed between BC cell lines and normal breast HMEC cells. From these, 110 miRNAs were common to BC subtypes. The miRNome enrichment analysis and interaction maps highlighted epigenetic-related pathways shared by all BC cell lines and revealed potential miRNA targets. Quantitative evaluation of BC patient samples and GETx/TCGA-BRCA datasets confirmed MYB and EZH2 as potential targets from BC miRNome. Moreover, overall survival was impacted by EZH2 expression. The expression of 15 miRNAs, selected according to aggressiveness of BC subtypes, was confirmed in TCGA-BRCA dataset. Of these miRNAs, miRNA-mRNA interaction prediction revealed 7 novel or underexplored miRNAs in BC: miR-1271-5p, miR-130a-5p, and miR-134 as MYB regulators and miR-138-5p, miR-455-3p, miR-487a, and miR-487b as EZH2 regulators. Herein, we report a novel molecular miRNA signature for BC and identify potential miRNA/mRNAs involved in disease subtypes.