The Breast Cancer Oncogene EMSY Represses Transcription of Antimetastatic MicroRNA MiR-31

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2014 Mar 4

PMID 24582497

Citations 34

Authors

Emmanuelle Vire

Christina Curtis

Veronica Davalos

Anna Git

Samuel Robson

Alberto Villanueva

August Vidal

Isaia Barbieri

Samuel Aparicio

Manel Esteller

Carlos Caldas

Tony Kouzarides

Affiliations

Soon will be listed here.

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.

Citing Articles

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EMSY inhibits homologous recombination repair and the interferon response, promoting lung cancer immune evasion.

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