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Proteomic analysis of EZH2 downstream target proteins in hepatocellular carcinoma
Author(s) -
Chen Yangchao,
Lin Marie Chiami,
Wang Hua,
Chan Chuyan,
Jiang Lei,
Ngai Sai Ming,
Yu Jun,
He Mingliang,
Shaw PangChui,
Yew David T.,
Sung Joseph J.,
Kung Hsiangfu
Publication year - 2007
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200700019
Subject(s) - ezh2 , gene knockdown , downregulation and upregulation , carcinogenesis , rna interference , biology , cancer research , microbiology and biotechnology , chemistry , cell culture , rna , epigenetics , cancer , biochemistry , genetics , gene
Enhancer of zeste homolog 2 (EZH2) is suggested to be a potential therapeutic target and a diagnostic marker for cancer. Our previous study also showed the critical role of EZH2 in hepatocellular carcinoma (HCC) tumorigenesis. The present study is aimed at revealing the comprehensive downstream pathways of EZH2 by functional proteomic profiling. Lentivirus mediated RNA interference (RNAi) was employed to knockdown EZH2 in HCC cells. The 2‐DE was employed to compare the expression profile difference between parental and EZH2‐knockdown HCC cells. In total, 28 spots were differentially expressed during EZH2 inhibition. Among all, 18 proteins were identified by PMF with MALDI‐TOF MS. Western blotting further validated upregulation of 60S acidic ribosomal protein P0 (L10E), and downregulation of two proteins with EZH2 inhibition: stathmin1 and probable protein disulfide isomerase (PDI) ER‐60 precursor (ERp57). Moreover, L10E was downregulated with overexpression of EZH2 in hepatocytes, and L10E reversed the effect of EZH2 on cell proliferation, suggesting it a downstream target of EZH2. The comprehensive and comparative analyses of proteins associated with EZH2 could further our understanding on the downstream signal cascade of EZH2 leading to tumorigenesis.