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ENO1 promotes liver carcinogenesis through YAP1-dependent arachidonic acid metabolism

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·2023·Nature Chemical Biology
DOI 10.1038/s41589-023-01391-6
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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 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.

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  • ENO1 can act as an RNA-binding protein to promote mRNA degradation of IRP1 or mRNA translation of YAP1, thereby suppressing ferroptosis and enhancing arachidonic acid metabolism, leading to tumour progression.

    “We recently reported that ENO1 can act as an RNA-binding protein to promote the messenger RNA (mRNA) degradation of iron-regulating protein (IRP1) or mRNA translation of yes-associated protein (YAP1), thereby suppressing ferroptosis and enhancing arachidonic acid metabolism, leading to tumour progression (Zhang et al., 2022a; Sun et al., 2023).”

    From ENO1–BACE2-mediated LDLR cleavage promotes liver cancer progression by remodelling cholesterol metabolism (2025) · cites this paper as Sun et al., 2023

  • ENO1 binds to and promotes the translation of YAP1 mRNA, promoting liver carcinogenesis by activating arachidonic acid metabolism and PGE2 accumulation.

    “ENO1 binds to and promotes the translation of YAP1 mRNA, promoting liver carcinogenesis by activating arachidonic acid metabolism and PGE2 accumulation”

    From ENO1–BACE2-mediated LDLR cleavage promotes liver cancer progression by remodelling cholesterol metabolism (2025) · cites this paper as Sun et al., 2023

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Metadata

Authors
Sun, L., Suo, C., Zhang, T., Shen, S., Gu, X., Qiu, S., Zhang, P., Wei, H., Ma, W., Yan, R., Chen, R., Jia, W., Cao, J., Zhang, H., & Gao, P.
ORCID
Venue
Nature Chemical Biology
Publisher
Springer Science and Business Media LLC
Published
2023-07-27
Volume
19
Issue
12
Pages
1492-1503
ISSN
  • 1552-4450
  • 1552-4469
DOI
10.1038/s41589-023-01391-6
Cited by
94
References
9
Language
en
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