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Mol Cell. 2014 Mar 6;53(5):806-18. doi: 10.1016/j.molcel.2014.01.029. Epub 2014 Feb 27.

The breast cancer oncogene EMSY represses transcription of antimetastatic microRNA miR-31.

Author information

1
Gurdon Institute and Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
2
Department of Oncology and Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, CB2 0RE, UK.
3
Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona 08907, Spain.
4
Department of Pathological Anatomy, Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona 08907, Spain.
5
Department of Molecular Oncology, British Columbia Cancer Agency, 675 West 10(th) Avenue, V5Z 1L3 Vancouver, Canada.
6
Department of Oncology and Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, CB2 0RE, UK; Cambridge Breast Unit, Addenbrooke's Hospital, Cambridge University Hospital, NHS Foundation Trust and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 2QQ, UK; Cambridge Experimental Cancer Medicine Centre (ECMC), Cambridge CB2 0RE, UK.
7
Gurdon Institute and Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK. Electronic address: t.kouzarides@gurdon.cam.ac.uk.

Erratum in

  • Mol Cell. 2014 Apr 10;54(1):203. Barbieri, Isaia [added].

Abstract

Amplification of the EMSY gene in sporadic breast and ovarian cancers is a poor prognostic indicator. Although EMSY has been linked to transcriptional silencing, its mechanism of action is unknown. Here, we report that EMSY acts as an oncogene, causing the transformation of cells in vitro and potentiating tumor formation and metastatic features in vivo. We identify an inverse correlation between EMSY amplification and miR-31 expression, an antimetastatic microRNA, in the METABRIC cohort of human breast samples. Re-expression of miR-31 profoundly reduced cell migration, invasion, and colony-formation abilities of cells overexpressing EMSY or haboring EMSY amplification. We show that EMSY is recruited to the miR-31 promoter by the DNA binding factor ETS-1, and it represses miR-31 transcription by delivering the H3K4me3 demethylase JARID1b/PLU-1/KDM5B. Altogether, these results suggest a pathway underlying the role of EMSY in breast cancer and uncover potential diagnostic and therapeutic targets in sporadic breast cancer.

PMID:
24582497
PMCID:
PMC3988886
DOI:
10.1016/j.molcel.2014.01.029
[Indexed for MEDLINE]
Free PMC Article
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