c-MYC inhibition impairs hypoxia response in glioblastoma multiforme
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Maria Patrizia Mongiardi1,*, Mauro Savino2,*, Maria Laura Falchetti1, Barbara Illi2, Francesca Bozzo3,4, Cristiana Valle1,4, Manuela Helmer-Citterich5, Fabrizio Ferrè6, Sergio Nasi2,**, Andrea Levi1,**
1Institute of Cell Biology and Neurobiology, CNR, c/o CERC, 00143 Rome, Italy
2Nucleic Acids Laboratory, Institute of Molecular Biology and Pathology, National Research Council (IBPM-CNR) and Department of Biology and Biotechnologies, Sapienza University, 00185 Rome, Italy
3Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy
4Fondazione Santa Lucia IRCCS, c/o CERC, 00143 Rome, Italy
5Centre for Molecular Bioinformatics, Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy
6Department of Pharmacy and Biotechnology (FaBiT), University of Bologna Alma Mater, 40126 Bologna, Italy
*These two authors contributed equally to this work
Maria Patrizia Mongiardi, e-mail: firstname.lastname@example.org
Andrea Levi, e-mail: email@example.com
Keywords: HIF, c-MYC, hypoxia, glycolysis, glioblastoma
Received: January 7, 2016 Accepted: March 31, 2016 Published: April 22, 2016
The c-MYC oncoprotein is a DNA binding transcription factor that enhances the expression of many active genes. c-MYC transcriptional signatures vary according to the transcriptional program defined in each cell type during differentiation. Little is known on the involvement of c-MYC in regulation of gene expression programs that are induced by extracellular cues such as a changing microenvironment. Here we demonstrate that inhibition of c-MYC in glioblastoma multiforme cells blunts hypoxia-dependent glycolytic reprogramming and mitochondria fragmentation in hypoxia. This happens because c-MYC inhibition alters the cell transcriptional response to hypoxia and finely tunes the expression of a subset of Hypoxia Inducible Factor 1-regulated genes. We also show that genes whose expression in hypoxia is affected by c-MYC inhibition are able to distinguish the Proneural subtype of glioblastoma multiforme, thus potentially providing a molecular signature for this class of tumors that are the least tractable among glioblastomas.
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