ENO1 Promotes Liver Carcinogenesis Through YAP1-dependent Arachidonic Acid Metabolism

Overview

Journal Nat Chem Biol

Specialties Biochemistry
Biology
Chemistry

Date 2023 Jul 27

PMID 37500770

Authors

Linchong Sun

Caixia Suo

Tong Zhang

Shengqi Shen

Xuemei Gu

Shiqiao Qiu

Pinggen Zhang

Haoran Wei

Wenhao Ma

Ronghui Yan

Rui Chen

Weidong Jia

Jie Cao

Huafeng Zhang

Ping Gao

Affiliations

Soon will be listed here.

Abstract

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 (PGE) 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.

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