title: 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.
authors.affiliation: Shanghai Center for Systems Biomedicine, State Key laboratory on Oncogenes and Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Rd., Shanghai 200240, China. xiaodongzhao@sjtu.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qi
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.forename: Yani
authors.initials: Y
authors.lastname: Kang
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.forename: Bingya
authors.initials: B
authors.lastname: Liu
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Shao
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhao
mesh_terms: D017317:Annexin A6 / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D015894:Genome, Human; D006657:Histones / Q000378:metabolism; D006801:Humans; D063151:Polycomb Repressive Complex 2 / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D017317:Annexin A6; D006657:Histones; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2