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The Human Epigenetic Drug Database (HEDD) is a comprehensive web-based database for epigenetic drugs, which focuses on the storage and integration of epigenetic drug datasets that were obtained from laboratory experiments that is essential for understanding the mechanism of action of these epigenetic drugs at a systematic level.

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DZNep-treated glioblastoma multiforme cancer stem cells

Drug Name:3-Deazaneplanocin A
Drug Category:HMTi
Sample Type:glioblastoma multiforme (GBM)cancer stem cells
Condition:glioblastoma multiforme (GBM)cancer
Experiment Type:Expression profiling by array
Experiment Platform:GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Description:Overexpression of the polycomb group protein enhancer of zeste homologue 2 (EZH2) occurs in diverse malignancies, including prostate cancer, breast cancer, and glioblastoma multiforme (GBM). Based on its ability to modulate transcription of key genes implicated in cell cycle control, DNA repair, and cell differentiation, EZH2 is believed to play a crucial role in tissue-specific stem cell maintenance and tumor development. Here, we show that targeted pharmacologic disruption of EZH2 by the S-adenosylhomocysteine hydrolase inhibitor 3-deazaneplanocin A (DZNep), or its specific downregulation by short hairpin RNA (shRNA), strongly impairs GBM cancer stem cell (CSC) self-renewal in vitro and tumor-initiating capacity in vivo. Using genome-wide expression analysis of DZNep-treated GBM CSCs, we found the expression of c-myc, recently reported to be essential for GBM CSCs, to be strongly repressed upon EZH2 depletion. Specific shRNA-mediated downregulation of EZH2 in combination with chromatin immunoprecipitation experiments revealed that c-myc is a direct target of EZH2 in GBM CSCs. Taken together, our observations provide evidence that direct transcriptional regulation of c-myc by EZH2 may constitute a novel mechanism underlying GBM CSC maintenance and suggest that EZH2 may be a valuable new therapeutic target for GBM management.
PubmedID:19934320
Citation:Suvà ML; Riggi N;Janiszewska M;Radovanovic I;Provero P;Stehle JC;Baumer K;Le Bitoux MA;Marino D;Cironi L;Marquez VE;Clément V;Stamenkovic I. EZH2 is essential for glioblastoma cancer stem cell maintenance. Cancer Res 2009 Dec 15;69(24):9211-8.
Downlaod:File Download (35.371MB)

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The Human Epigenetic Drug Database (HEDD) is a comprehensive web-based database for epigenetic drugs, which focuses on integrating epigenetic drug studies based Omics data from high through experiments that is essential for understanding the mechanism of action of these epigenetic drugs at a systematic level.

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©2016 Group of Computational Epigenomics and Bioinformatics, College of Life Science, Jilin Normal University, China

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