Overexpression of ONECUT1 suppresses hepatoblastoma progression via modulating tumor cell growth and tumor microenvironment
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Le résumé fourni par la source
BACKGROUND: Hepatoblastoma is the most common malignant liver tumor in children. Our previous work showed that enforced expression of the transcription factor One Cut Homeobox 1 (ONECUT1) suppresses the initiation of hepatoblastoma. However, it remains unclear whether increasing ONECUT1 expression can also inhibit tumor progression after tumors have already formed. The purpose of this study was to determine the effects of ONECUT1 induction on tumor cell behavior and tumor growth during established hepatoblastoma progression. RESULTS: We generated doxycycline-inducible expression systems to upregulate ONECUT1 in hepatoblastoma cells in culture and in mouse models. In human hepatoblastoma cells, induction of ONECUT1 promoted apoptotic cell death and reduced cell cycle progression. In a subcutaneous xenograft model using immunodeficient mice, ONECUT1 induction slowed tumor growth but did not cause tumor regression. We then established an orthotopic HB model in FVB/N mice by tail-vein injection of YAP/β-catenin/TRE-ONECUT1 plasmids. ONECUT1 expression in existing mouse HB cells was induced by feeding the mice with DOX-water. Remarkably, tumor regression was observed following ONECUT1 induction. Histological analyses showed extensive necrosis and apoptosis in tumor lesions following induction of ONECUT1, accompanied by robust macrophage infiltration and moderate T cell infiltration. Depletion of T cells using antibodies against CD4 and CD8 weakened the antitumor effect of ONECUT1, indicating that T-cell activity contributes to tumor suppression. Transcriptomic analysis further suggested that ONECUT1 may promote antitumor immune responses in part by increasing expression of immune-related cytokines. CONCLUSIONS: Induction of ONECUT1 suppresses hepatoblastoma progression by inhibiting tumor cell growth and by reshaping the tumor immune microenvironment. These findings reveal a previously unrecognized antitumor role of ONECUT1 during hepatoblastoma progression and suggest that restoring ONECUT1 activity may represent a promising therapeutic strategy for this pediatric malignancy.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Overexpression of ONECUT1 suppresses hepatoblastoma progression via modulating tumor cell growth and tumor microenvironment
- Date Crossref
- 05/04/2026
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
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University of Hawaiʻi at Mānoa pays non établi dans la noticeUniversité ou école supérieure
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University of Hawaii System pays non établi dans la noticeUniversité ou école supérieure
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Chinese Academy of Medical Sciences & Peking Union Medical College pays non établi dans la noticeUniversité ou école supérieure
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University of Hawaiʻi at Mānoa, University of Hawaii System et Chinese Academy of Medical Sciences & Peking Union Medical College, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.