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Status |
Public on May 19, 2023 |
Title |
ENO1 promotes liver carcinogenesis through YAP1-dependent arachidonic acid metabolism |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing Other
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Summary |
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 E2 (PGE2) 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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Overall design |
RNA immunoprecipitation sequencing (RIP-seq) analysis in HEK293T cells overexpressing ENO1, primary antibodies against ENO1 (11204-1-AP, Proteintech) were used in the RIP-seq assay. PLC cells with ENO1 or YAP1 knockdown were cultured with DMEM, then total RNA was extracted using Trizol Reagent followed by RNA-seq to identify the co-regulated genes by ENO1 and YAP1.
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Web link |
https://www.nature.com/articles/s41589-023-01391-6
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Contributor(s) |
Sun L, Shen S, Zhang H, Gao P |
Citation(s) |
37500770 |
Submission date |
Sep 08, 2021 |
Last update date |
Aug 18, 2023 |
Contact name |
Linchong Sun |
E-mail(s) |
sunlc@mail.ustc.edu.cn
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Organization name |
South China University of China
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Street address |
B2 Building, South China University of Technology, No. 382, Waihuandong Road, Guangzhou Higher Education Mega Center, Panyu District
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City |
Guangzhou |
State/province |
Guangdong |
ZIP/Postal code |
510006 |
Country |
China |
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Platforms (1) |
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Samples (5)
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Relations |
BioProject |
PRJNA761712 |
SRA |
SRP336203 |