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

Emmanuelle Viré, Christina Curtis, Veronica Davalos, Anna Git, Samuel Robson, Alberto Villanueva, August Vidal, Isaia Barbieri, Samuel Aparicio, Manel Esteller, Carlos Caldas, Tony Kouzarides

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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.
Original languageEnglish
Pages (from-to)806-818
Number of pages13
JournalMolecular Cell
Volume53
Issue number5
Early online date27 Feb 2014
DOIs
Publication statusPublished - 1 Mar 2014

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