G-protein-coupled receptor GPR17 inhibits glioma development by increasing polycomb repressive complex 1-mediated ROS production.
G-protein-coupled receptor GPR17 inhibits glioma development by increasing polycomb repressive complex 1-mediated ROS production.
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G蛋白偶联受体GPR17通过增加Polycomb抑制复合物1介导的ROS产生来抑制神经胶质瘤的发育。
DOI：
10.1038/s41419-021-03897-0
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发表时间：
2021-06-12
影响因子：
9
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Liu H;Xing R;Ou Z;Zhao J;Hong G;Zhao TJ;Han Y;Chen Y
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.
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影响因子：
29
作者：
Cheng, Xiang;Geng, Feng;Guo, Deliang
通讯作者：
Guo, Deliang
影响因子：
25
作者：
Chen, Ying;Wu, Heng;Wang, Shuzong;Koito, Hisami;Li, Jianrong;Ye, Feng;Hoang, Jenny;Escobar, Sabine S.;Gow, Alexander;Arnett, Heather A.;Trapp, Bruce D.;Karandikar, Nitin J.;Hsieh, Jenny;Lu, Q. Richard
通讯作者：
Lu, Q. Richard
DOI：
10.1038/nrd.2017.178
发表时间：
2017-12
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Hauser AS;Attwood MM;Rask-Andersen M;Schiöth HB;Gloriam DE
通讯作者：
Gloriam DE
影响因子：
82.9
作者：
Chang J;Mancuso MR;Maier C;Liang X;Yuki K;Yang L;Kwong JW;Wang J;Rao V;Vallon M;Kosinski C;Zhang JJ;Mah AT;Xu L;Li L;Gholamin S;Reyes TF;Li R;Kuhnert F;Han X;Yuan J;Chiou SH;Brettman AD;Daly L;Corney DC;Cheshier SH;Shortliffe LD;Wu X;Snyder M;Chan P;Giffard RG;Chang HY;Andreasson K;Kuo CJ
通讯作者：
Kuo CJ
影响因子：
37.3
作者：
Cho EA;Kim EJ;Kwak SJ;Juhnn YS
通讯作者：
Juhnn YS