2. Academic Validation
  3. 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

  • Cell Death Dis. 2021 Jun 12;12(6):610. doi: 10.1038/s41419-021-03897-0.
Huiqing Liu  # 1,  Rui Xing  # 1,  Zhimin Ou  # 1,  Junying Zhao 1,  Guolin Hong 2 3,  Tong-Jin Zhao 4,  Ying Han 5 6,  Ying Chen 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian Province, China.
  • 2 The Department of Laboratory Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, China.
  • 3 Xiamen Key Laboratory of Genetic Testing, Xiamen, Fujian Province, China.
  • 4 Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China.
  • 5 The Department of Laboratory Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, China. hanyingatu@163.com.
  • 6 Xiamen Key Laboratory of Genetic Testing, Xiamen, Fujian Province, China. hanyingatu@163.com.
  • 7 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian Province, China. yingchen@xmu.edu.cn.
  • # Contributed equally.
PMID: 34120140 DOI: 10.1038/s41419-021-03897-0
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.

Figures
Products
Inhibitors & Agonists
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z