TY - JOUR
T1 - Proteomic analysis of EZH2 downstream target proteins in hepatocellular carcinoma
AU - Chen, Yangchao
AU - Lin, Marie Chia-Mi
AU - Wang, Hua
AU - Chan, Chu-Yan
AU - Jiang, Lei
AU - Sai, Ming Ngai
AU - Yu, Jun
AU - He, Ming-Liang
AU - Shaw, Pang-Chui
AU - Yew, David T.
AU - Sung, Joseph J.
AU - Kung, Hsiang-Fu
PY - 2007/9
Y1 - 2007/9
N2 - 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. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.
AB - 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. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.
KW - Enhancer of zeste homolog 2
KW - Hepatocellular carcinoma
KW - Target gene
UR - http://www.scopus.com/inward/record.url?scp=34748893835&partnerID=8YFLogxK
UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-34748893835&origin=recordpage
U2 - 10.1002/pmic.200700019
DO - 10.1002/pmic.200700019
M3 - RGC 21 - Publication in refereed journal
C2 - 17676662
SN - 1615-9853
VL - 7
SP - 3097
EP - 3104
JO - Proteomics
JF - Proteomics
IS - 17
ER -
