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Histone demethylase PHF8 promotes epithelial to mesenchymal transition and breast tumorigenesis.

Nucleic Acids Res.. 2016-11; 
Shao P, Liu Q, Maina PK, Cui J, Bair TB, Li T, Umesalma S, Zhang W, Qi HH. Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, IA 52242, USA.
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摘要

Histone demethylase PHF8 is upregulated and plays oncogenic roles in various cancers; however, the mechanisms underlying its dysregulation and functions in carcinogenesis remain obscure. Here, we report the novel functions of PHF8 in EMT (epithelial to mesenchymal transition) and breast cancer development. Genome-wide gene expression analysis revealed that PHF8 overexpression induces an EMT-like process, including the upregulation of SNAI1 and ZEB1. PHF8 demethylates H3K9me1, H3K9me2 and sustains H3K4me3 to prime the transcriptional activation of SNAI1 by TGF-β signaling. We show that PHF8 is upregulated and positively correlated with MYC at protein levels in breast cancer. MYC post-transcriptionally regul... More

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