G-protein-coupled receptor GPR17 inhibits glioma development by increasing polycomb repressive complex 1-mediated ROS production.

Cell Death & Disease
Huiqing LiuYing Chen

Abstract

Glioma is the most common primary tumor in the central nervous system. However, the development of glioma and effective therapeutic strategies remain elusive. Here, we identify GPR17 as a potential target to treat glioma. Data mining with human LGG and GBM samples reveals that GPR17 is negatively correlated with glioma development. Overexpressing GPR17 inhibits glioma cell proliferation and induces apoptosis by raising ROS levels. GPR17-overexpressing glioma cells are less tumorigenic in the brain than in control cells. Mechanistically, GPR17 inhibits the transcription of RNF2, a key component in the PRC1 complex, through cAMP/PKA/NF-κB signaling, leading to reduced histone H2A monoubiquitination. ChIP-Seq and RNA-Seq analyses reveal KLF9 as a direct target of RNF2. KLF9 mediates the functions of GPR17 and RNF2 in glioma cells. Furthermore, activation of GPR17 by its agonist inhibits glioma formation. Our findings have thus identified GPR17 as a key regulator of glioma development and a potential therapeutic target for gliomas.

References

Jul 10, 2007·Acta Neuropathologica·David N LouisPaul Kleihues
Aug 2, 2008·The New England Journal of Medicine·Patrick Y Wen, Santosh Kesari
Sep 5, 2008·PLoS Computational Biology·Ronald C TaylorShyam Biswal
Sep 10, 2009·Nature Reviews. Molecular Cell Biology·Jeffrey A Simon, Robert E Kingston
Sep 8, 2012·Reproduction : the Official Journal of the Society for the Study of Fertility·Mazdak SalavatiAli A Fouladi-Nashta
Jan 16, 2013·Proceedings of the National Academy of Sciences of the United States of America·Wen-jing SuJian Zhang
Aug 2, 2013·The Journal of Biological Chemistry·Ismail Hassan IsmailMichael J Hendzel
Sep 21, 2013·Nature·Corbin E Meacham, Sean J Morrison
Feb 28, 2014·International Journal of Molecular Medicine·Woon-Won Jung
Mar 13, 2014·Molecular Cell·Shoshanna N ZuckerMikhail A Nikiforov
Oct 7, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jinlong ShiJian Chen
May 31, 2015·Journal of Experimental & Clinical Cancer Research : CR·Li-sen QinShi-ming Zhang
Oct 6, 2015·Nature Medicine·Lindsay M LaFaveRoss L Levine
Oct 10, 2015·Cancer Discovery·Kunal RaiLynda Chin
Dec 15, 2015·Science Advances·Sergi ArandaLuciano Di Croce
Oct 14, 2016·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Zhimin OuYing Chen
May 20, 2017·Current Medicinal Chemistry·Ron BatashMoshe Schaffer
Sep 25, 2017·Cell·Bernd SchuettengruberGiacomo Cavalli
Oct 28, 2017·Nature Reviews. Drug Discovery·Alexander S HauserDavid E Gloriam
Jan 22, 2019·Oncogene·Archis BagatiMikhail A Nikiforov
Feb 26, 2019·Free Radical Biology & Medicine·Anna Rita FetoniDiana Troiani
Mar 27, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yang LiWei Zhuo

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limma
BigWig
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deepTools
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