ACSL4 promotes the formation of the proliferative subtype in hepatoblastoma
Abstract Hepatoblastoma (HB) is the most common pediatric liver malignancy, with its significant heterogeneity complicating the identification of the most aggressive subtypes and the development of targeted therapies. In this study, we performed transcriptomic analysis of HB samples from the GEO dat...
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BMC
2025-02-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-025-13592-4 |
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| author | Wei Dang Qin Li Xiaoying Wang |
| author_facet | Wei Dang Qin Li Xiaoying Wang |
| author_sort | Wei Dang |
| collection | DOAJ |
| description | Abstract Hepatoblastoma (HB) is the most common pediatric liver malignancy, with its significant heterogeneity complicating the identification of the most aggressive subtypes and the development of targeted therapies. In this study, we performed transcriptomic analysis of HB samples from the GEO database and identified three distinct molecular subtypes with varying prognostic outcomes. Among them, the proliferative subtype, characterized by enhanced proliferative capacity, poor prognosis, and an immunosuppressive tumor microenvironment, was particularly notable. ACSL4 emerged as a critical biomarker of this proliferative subtype, driving HB cell proliferation both in vitro and in vivo. Furthermore, pharmacological inhibition of ACSL4 using abemaciclib significantly suppressed tumor growth in xenograft models. Mechanistically, ACSL4 was found to promote cell proliferation by downregulating the interferon response signaling pathway which may implicate contribution to immunosuppression in the tumor. These findings underscore the pivotal role of ACSL4 in HB progression and highlight its potential as a therapeutic target for aggressive HB subtypes. |
| format | Article |
| id | doaj-art-bf5815872071404395fff11b1a857f9d |
| institution | Kabale University |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-bf5815872071404395fff11b1a857f9d2025-02-09T12:41:34ZengBMCBMC Cancer1471-24072025-02-0125111310.1186/s12885-025-13592-4ACSL4 promotes the formation of the proliferative subtype in hepatoblastomaWei Dang0Qin Li1Xiaoying Wang2Department of Liver Surgery and Transplantation and Key Laboratory of Carcinogenesis and Cancer Invasion, Zhongshan Hospital, Ministry of Education, Liver Cancer Institute, Fudan UniversityDepartment of Pathology, Institute of Pathology, Fudan University Shanghai Cancer Center, Fudan UniversityDepartment of Liver Surgery and Transplantation and Key Laboratory of Carcinogenesis and Cancer Invasion, Zhongshan Hospital, Ministry of Education, Liver Cancer Institute, Fudan UniversityAbstract Hepatoblastoma (HB) is the most common pediatric liver malignancy, with its significant heterogeneity complicating the identification of the most aggressive subtypes and the development of targeted therapies. In this study, we performed transcriptomic analysis of HB samples from the GEO database and identified three distinct molecular subtypes with varying prognostic outcomes. Among them, the proliferative subtype, characterized by enhanced proliferative capacity, poor prognosis, and an immunosuppressive tumor microenvironment, was particularly notable. ACSL4 emerged as a critical biomarker of this proliferative subtype, driving HB cell proliferation both in vitro and in vivo. Furthermore, pharmacological inhibition of ACSL4 using abemaciclib significantly suppressed tumor growth in xenograft models. Mechanistically, ACSL4 was found to promote cell proliferation by downregulating the interferon response signaling pathway which may implicate contribution to immunosuppression in the tumor. These findings underscore the pivotal role of ACSL4 in HB progression and highlight its potential as a therapeutic target for aggressive HB subtypes.https://doi.org/10.1186/s12885-025-13592-4HepatoblastomaMolecular subtypingACSL4Cell-cell communicationAbemaciclib |
| spellingShingle | Wei Dang Qin Li Xiaoying Wang ACSL4 promotes the formation of the proliferative subtype in hepatoblastoma BMC Cancer Hepatoblastoma Molecular subtyping ACSL4 Cell-cell communication Abemaciclib |
| title | ACSL4 promotes the formation of the proliferative subtype in hepatoblastoma |
| title_full | ACSL4 promotes the formation of the proliferative subtype in hepatoblastoma |
| title_fullStr | ACSL4 promotes the formation of the proliferative subtype in hepatoblastoma |
| title_full_unstemmed | ACSL4 promotes the formation of the proliferative subtype in hepatoblastoma |
| title_short | ACSL4 promotes the formation of the proliferative subtype in hepatoblastoma |
| title_sort | acsl4 promotes the formation of the proliferative subtype in hepatoblastoma |
| topic | Hepatoblastoma Molecular subtyping ACSL4 Cell-cell communication Abemaciclib |
| url | https://doi.org/10.1186/s12885-025-13592-4 |
| work_keys_str_mv | AT weidang acsl4promotestheformationoftheproliferativesubtypeinhepatoblastoma AT qinli acsl4promotestheformationoftheproliferativesubtypeinhepatoblastoma AT xiaoyingwang acsl4promotestheformationoftheproliferativesubtypeinhepatoblastoma |