The shaping and functional consequences of the microRNA landscape in breast cancer

Abstract

MicroRNAs (miRNAs) show differential expression across breast cancer subtypes, and have both oncogenic and tumour-suppressive roles. Here we report the miRNA expression profiles of 1,302 breast tumours with matching detailed clinical annotation, long-term follow-up and genomic and messenger RNA expression data. This provides a comprehensive overview of the quantity, distribution and variation of the miRNA population and provides information on the extent to which genomic, transcriptional and post-transcriptional events contribute to miRNA expression architecture, suggesting an important role for post-transcriptional regulation. The key clinical parameters and cellular pathways related to the miRNA landscape are characterized, revealing context-dependent interactions, for example with regards to cell adhesion and Wnt signalling. Notably, only prognostic miRNA signatures derived from breast tumours devoid of somatic copy-number aberrations (CNA-devoid) are consistently prognostic across several other subtypes and can be validated in external cohorts. We then use a data-driven approach to seek the effects of miRNAs associated with differential co-expression of mRNAs, and find that miRNAs act as modulators of mRNA-mRNA interactions rather than as on-off molecular switches. We demonstrate such an important modulatory role for miRNAs in the biology of CNA-devoid breast cancers, a common subtype in which the immune response is prominent. These findings represent a new framework for studying the biology of miRNAs in human breast cancer.

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

“…In addition, De Rinaldis et al 32 identified a 46-miRNA signature that could be used to differentiate between breast cancer subtypes. Dvinge et al 33 also obtained similar findings in their research. In a meta-analysis of independent trials, van Schooneveld et al described various subtype-specific miRNAs.…”

miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives

“…Invasive lung carcinoma is characterised by the presence of many various genetic and epigenetic alterations in tumour cells [80]. This leads to deregulated expression of certain miRNAs [81], resulting in significant changes in their concentrations and compositions and, consequently, their activities (described as miRNA under-or overexpression), and these miRNAs are potential biomarkers of clinical relevance [82,83]. Previous studies have confirmed the usefulness of miRNAs as biomarkers of NSCLC [48,[84][85][86].…”

The locus of microRNA-10b

“…(A) Kaplan-Meier analysis based on the MetaBriC mir expression data. 43 Survival of the 370 patients with the highest (top third) expression levels of mir-10b* (red line) was compared with the 370 patients with the lowest expression levels (blue line). the plot was truncated at 15 y, P value is indicated in the title.…”