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

# metadata.dc.description.abstract[].value
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.

# metadata.dc.rights[].value
cc-by-nc-nd (c) Delgado, M. Eugenia et al., 2025

# metadata.dc.source[].value
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

# metadata.dc.title[].value
CPEB4 modulates liver cancer progression by translationally regulating hepcidin expression and sensitivity to ferroptosis