ENO1 promotes liver carcinogenesis through YAP1-dependent arachidonic acid metabolism

作者：Sun, Linchong^*; Suo, Caixia; Zhang, Tong; Shen, Shengqi; Gu, Xuemei; Qiu, Shiqiao; Zhang, Pinggen; Wei, Haoran; Ma, Wenhao; Yan, Ronghui; Chen, Rui; Jia, Weidong; Cao, Jie; Zhang, Huafeng^*; Gao, Ping^*

来源：Nature Chemical Biology, 2023, 19(12): 1492-+.

DOI：10.1038/s41589-023-01391-6

• COLI RNA DEGRADOSOME
• PHOSPHOLIPASE A(2)
• ALPHA-ENOLASE
• CANCER
• YAP
• ASPIRIN
• PATHWAY
• EXPRESSION
• PROTEINS
• ROLES

Enolase 1 (ENO1) is a glycolytic enzyme that plays essential roles in various pathological activities including cancer development. However, the mechanisms underlying ENO1-contributed tumorigenesis are not well explained. Here, we uncover that ENO1, as an RNA-binding protein, binds to the cytosine-uracil-guanine-rich elements of YAP1 messenger RNA to promote its translation. ENO1 and YAP1 positively regulate alternative arachidonic acid (AA) metabolism by inverse regulation of PLCB1 and HPGD (15-hydroxyprostaglandin dehydrogenase). The YAP1/PLCB1/HPGD axis-mediated activation of AA metabolism and subsequent accumulation of prostaglandin E-2 (PGE(2)) are responsible for ENO1-mediated cancer progression, which can be retarded by aspirin. Finally, aberrant activation of ENO1/YAP1/PLCB1 and decreased HPGD expression in clinical hepatocellular carcinoma samples indicate a potential correlation between ENO1-regulated AA metabolism and cancer development. These findings underline a new function of ENO1 in regulating AA metabolism and tumorigenesis, suggesting a therapeutic potential for aspirin in patients with liver cancer with aberrant expression of ENO1 or YAP1.

• 单位
  广东省心血管病研究所; 南方医科大学; 1; 广东省人民医院; 中国科学院