The shaping and functional consequences of the microRNA landscape in breast cancer.
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| Title: | The shaping and functional consequences of the microRNA landscape in breast cancer. |
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| Authors: | Dvinge, Heidi, Git, Anna, Gräf, Stefan, Salmon-Divon, Mali, Curtis, Christina, Sottoriva, Andrea, Zhao, Yongjun, Hirst, Martin, Armisen, Javier, Miska, Eric A., Chin, Suet-Feung, Provenzano, Elena, Turashvili, Gulisa, Green, Andrew, Ellis, Ian, Aparicio, Sam, Caldas, Carlos |
| Source: | Nature. 5/16/2013, Vol. 497 Issue 7449, p378-382. 5p. 1 Diagram, 3 Graphs. |
| Subjects: | MicroRNA, Breast cancer, Gene expression, Oncogenes, Messenger RNA, Immune response |
| 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. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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