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Delgado et al_JHEP Rep_2025.pdf (2.37 MB)

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2025-03-03

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cc-by-nc-nd (c) Delgado, M. Eugenia et al., 2025
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/222546

CPEB4 modulates liver cancer progression by translationally regulating hepcidin expression and sensitivity to ferroptosis

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Background & Aims Liver cancer is a significant global health issue, with its incidence rising in parallel with the obesity epidemic. The limited therapeutic options available emphasize the need for a better understanding of the molecular pathways involved in its pathogenesis. While much of the previous research has focused on transcriptional changes, this study examines translational alterations, specifically the role of cytoplasmic polyadenylation element binding protein 4 (CPEB4), a key regulator of translation. Methods We analyzed publicly available patient databases and conducted studies using human and mouse liver cancer cells, xenograft and allograft models, mouse models of high-fat diet-related liver cancer, and CPEB4 knockout and knockdown mice and cell lines. Results Patient data analysis (n = 87) showed a strong correlation between low CPEB4 levels and reduced survival rates (p <0.001). In mouse models of diet-induced liver cancer (n = 10–15 per group), both systemic and hepatocyte-specific CPEB4 knockout mice exhibited significantly increased tumor burden compared with wild-type controls (p <0.05). In vitro studies using human and murine liver cancer cells (n = 3 biological replicates) demonstrated reduced sensitivity to ferroptosis upon CPEB4 depletion when induced by erastin or RSL3 (p <0.01). Mechanistically, CPEB4 deficiency suppressed hepcidin expression, leading to elevated ferroportin levels, decreased intracellular iron accumulation, and reduced lipid peroxidation (p <0.05). Conclusions This study uncovers a novel CPEB4-dependent mechanism linking translational control to liver cancer progression and ferroptosis regulation. Therapeutic strategies targeting CPEB4-mediated pathways hold promise for advancing treatment options in liver cancer.

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Matèries

Càncer de fetge, Marcadors tumorals

Matèries (anglès)

Liver cancer, Tumor markers

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Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

DELGADO, M. eugenia, NARANJO SUÁREZ, Salvador, RAMIREZ PEDRAZA, Marta, CÁRDENAS, Beatriz i., GALLARDO MARTÍNEZ, Carmen, BALVEY GIL, Alexandra, BELLOC ROCASALBAS, Eulàlia, MARTÍN ORTEGA, Judit, BOYLE, Mark, MÉNDEZ DE LA IGLESIA, Raúl, FERNÁNDEZ LOBATO, Mercedes. CPEB4 modulates liver cancer progression by translationally regulating hepcidin expression and sensitivity to ferroptosis. _Jhep Reports_. 2025. Vol. 7, núm. 3, pàgs. 101296. [consulta: 25 de novembre de 2025]. ISSN: 2589-5559. [Disponible a: https://hdl.handle.net/2445/222546]

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