Journal
CELL DEATH & DISEASE
Volume 12, Issue 6, Pages -Publisher
SPRINGERNATURE
DOI: 10.1038/s41419-021-03897-0
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Funding
- National Natural Science Foundation of China [31771122, 81601080, 81772287]
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The overexpression of GPR17 in glioma cells inhibits cell proliferation, induces apoptosis, and decreases tumorigenic potential. By inhibiting transcription of RNF2, GPR17 reduces histone monoubiquitination and affects the function of KLF9 in glioma cells. Activation of GPR17 can suppress glioma formation, making it a potential therapeutic target.
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-kappa B 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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