Issue 7, 2015

Genome-wide transcriptional profiling analysis reveals annexin A6 as a novel EZH2 target gene involving gastric cellular proliferation

Abstract

A histone methyltransferase enhancer of zeste homologue 2 (EZH2) catalyzes trimethylation at histone H3 lysine27 (H3K27me3) and is frequently dysregulated in a wide range of human cancers. EZH2-mediated gene silencing contributes to carcinogenesis and regulates stem cell maintenance and differentiation; however, the underlining mechanisms remain to be completely understood. Here, we found that downregulation of EZH2 by RNA interference (RNAi) in gastric cancer cells suppresses cell growth, migration, invasion, and induces cell cycle arrest. Transcriptome analysis identified 1223 EZH2 responsive genes upon EZH2 knockdown. These genes are involved in the biological processes of cell cycle, proliferation and metastasis. Particularly, we found that annexin A6 (ANXA6) is a new target of EZH2 and is repressed in gastric cancer cells. Restoration of ANXA6 expression inhibits gastric cellular proliferation. We further demonstrated that EZH2-mediated H3K27me3, rather than promoter DNA methylation, is primarily responsible for ANXA6 inhibition. Taken together, our results provide a framework for understanding EZH2 biology and reveal ANXA6 as a new EZH2 target involving gastric cellular proliferation.

Graphical abstract: Genome-wide transcriptional profiling analysis reveals annexin A6 as a novel EZH2 target gene involving gastric cellular proliferation

Supplementary files

Article information

Article type
Paper
Submitted
03 Apr 2015
Accepted
24 Apr 2015
First published
24 Apr 2015

Mol. BioSyst., 2015,11, 1980-1986

Genome-wide transcriptional profiling analysis reveals annexin A6 as a novel EZH2 target gene involving gastric cellular proliferation

Y. Qi, X. Zhang, Y. Kang, J. Wu, J. Chen, H. Li, Y. Guo, B. Liu, Z. Shao and X. Zhao, Mol. BioSyst., 2015, 11, 1980 DOI: 10.1039/C5MB00233H

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