MARCH8 suppresses hepatocellular carcinoma by promoting SREBP1 degradation and modulating fatty acid de novo synthesis
Abstract Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors of the digestive system, and its prevalence is currently increasing. The current study aims to elucidate the mechanism by which membrane-associated RING-CH8 (MARCH8) impedes the progression of HCC. MARCH8 was ident...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-05-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07707-9 |
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| author | Dao-yuan Tu Rui Peng Sheng-jie Jin Bing-bing Su Song-song Fan Jia-hao Zhang Shun-yi Wang Yang-yang Miao Guo-qing Jiang Chi Zhang Jun Cao Dou-sheng Bai |
| author_facet | Dao-yuan Tu Rui Peng Sheng-jie Jin Bing-bing Su Song-song Fan Jia-hao Zhang Shun-yi Wang Yang-yang Miao Guo-qing Jiang Chi Zhang Jun Cao Dou-sheng Bai |
| author_sort | Dao-yuan Tu |
| collection | DOAJ |
| description | Abstract Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors of the digestive system, and its prevalence is currently increasing. The current study aims to elucidate the mechanism by which membrane-associated RING-CH8 (MARCH8) impedes the progression of HCC. MARCH8 was identified as a distinct prognostic marker for recurrence-free survival (RFS) and overall survival (OS) in patients with HCC. This study shows that MARCH8 hinders lipid deposition by suppressing the expression of key enzymes for the de novo synthesis of fatty acids (FAs) via RNA sequencing, untargeted metabolomics, and a series of in vivo and in vitro experiments. Further experimental validation demonstrated that MARCH8 was a novel E3 ligase of sterol regulatory element binding protein 1 (SREBP1). And, it primarily promoted the degradation of SREBP1, thereby suppressing the expression of key enzymes involved in the de novo synthesis of FAs. In conclusion, this study has identified MARCH8 as a key “switch” that can be targeted to prevent de novo FA synthesis in HCC cells. This finding may have substantial implications for discovering innovative therapeutic strategies for HCC. |
| format | Article |
| id | doaj-art-7d659a190e8c4f5bb721f142bf46b830 |
| institution | DOAJ |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-7d659a190e8c4f5bb721f142bf46b8302025-08-20T03:07:54ZengNature Publishing GroupCell Death and Disease2041-48892025-05-0116111610.1038/s41419-025-07707-9MARCH8 suppresses hepatocellular carcinoma by promoting SREBP1 degradation and modulating fatty acid de novo synthesisDao-yuan Tu0Rui Peng1Sheng-jie Jin2Bing-bing Su3Song-song Fan4Jia-hao Zhang5Shun-yi Wang6Yang-yang Miao7Guo-qing Jiang8Chi Zhang9Jun Cao10Dou-sheng Bai11Department of Hepatobiliary Surgery, Northern Jiangsu People’s Hospital Affiliated to Yangzhou UniversityDepartment of Hepatobiliary Surgery, Northern Jiangsu People’s Hospital Affiliated to Yangzhou UniversityDepartment of Hepatobiliary Surgery, Northern Jiangsu People’s Hospital Affiliated to Yangzhou UniversityDepartment of Hepatobiliary Surgery, Northern Jiangsu People’s Hospital Affiliated to Yangzhou UniversityDepartment of Hepatobiliary Surgery, Northern Jiangsu People’s Hospital Affiliated to Yangzhou UniversityDepartment of Hepatobiliary Surgery, Northern Jiangsu People’s Hospital Affiliated to Yangzhou UniversityDepartment of Hepatobiliary Surgery, Northern Jiangsu People’s Hospital Affiliated to Yangzhou UniversityDepartment of Hepatobiliary Surgery, Northern Jiangsu People’s Hospital Affiliated to Yangzhou UniversityDepartment of Hepatobiliary Surgery, Northern Jiangsu People’s Hospital Affiliated to Yangzhou UniversityDepartment of Hepatobiliary Surgery, Northern Jiangsu People’s Hospital Affiliated to Yangzhou UniversityDepartment of Hepatobiliary Surgery, Northern Jiangsu People’s Hospital Affiliated to Yangzhou UniversityDepartment of Hepatobiliary Surgery, Northern Jiangsu People’s Hospital Affiliated to Yangzhou UniversityAbstract Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors of the digestive system, and its prevalence is currently increasing. The current study aims to elucidate the mechanism by which membrane-associated RING-CH8 (MARCH8) impedes the progression of HCC. MARCH8 was identified as a distinct prognostic marker for recurrence-free survival (RFS) and overall survival (OS) in patients with HCC. This study shows that MARCH8 hinders lipid deposition by suppressing the expression of key enzymes for the de novo synthesis of fatty acids (FAs) via RNA sequencing, untargeted metabolomics, and a series of in vivo and in vitro experiments. Further experimental validation demonstrated that MARCH8 was a novel E3 ligase of sterol regulatory element binding protein 1 (SREBP1). And, it primarily promoted the degradation of SREBP1, thereby suppressing the expression of key enzymes involved in the de novo synthesis of FAs. In conclusion, this study has identified MARCH8 as a key “switch” that can be targeted to prevent de novo FA synthesis in HCC cells. This finding may have substantial implications for discovering innovative therapeutic strategies for HCC.https://doi.org/10.1038/s41419-025-07707-9 |
| spellingShingle | Dao-yuan Tu Rui Peng Sheng-jie Jin Bing-bing Su Song-song Fan Jia-hao Zhang Shun-yi Wang Yang-yang Miao Guo-qing Jiang Chi Zhang Jun Cao Dou-sheng Bai MARCH8 suppresses hepatocellular carcinoma by promoting SREBP1 degradation and modulating fatty acid de novo synthesis Cell Death and Disease |
| title | MARCH8 suppresses hepatocellular carcinoma by promoting SREBP1 degradation and modulating fatty acid de novo synthesis |
| title_full | MARCH8 suppresses hepatocellular carcinoma by promoting SREBP1 degradation and modulating fatty acid de novo synthesis |
| title_fullStr | MARCH8 suppresses hepatocellular carcinoma by promoting SREBP1 degradation and modulating fatty acid de novo synthesis |
| title_full_unstemmed | MARCH8 suppresses hepatocellular carcinoma by promoting SREBP1 degradation and modulating fatty acid de novo synthesis |
| title_short | MARCH8 suppresses hepatocellular carcinoma by promoting SREBP1 degradation and modulating fatty acid de novo synthesis |
| title_sort | march8 suppresses hepatocellular carcinoma by promoting srebp1 degradation and modulating fatty acid de novo synthesis |
| url | https://doi.org/10.1038/s41419-025-07707-9 |
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