Zbtb7b defines a compensatory mechanism in MASLD‐related HCC progression by suppressing H19‐mediated hepatic lipid deposition
Abstract Hepatocellular carcinoma (HCC) is a widely prevalent type of primary liver cancer. However, strategies for pretumor intervention are still limited. In this study, a liver‐specific Zbtb7b knockout mouse model was used to evaluate the role of Zbtb7b in metabolic dysfunction‐associated steatot...
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| Format: | Article |
| Language: | English |
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Wiley
2024-12-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.70160 |
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| author | Yinglin Han Kaimin Wu Xin Peng Yinkun Fu Wenyan Li Jing Ma He Jiang Xu‐Yun Zhao |
| author_facet | Yinglin Han Kaimin Wu Xin Peng Yinkun Fu Wenyan Li Jing Ma He Jiang Xu‐Yun Zhao |
| author_sort | Yinglin Han |
| collection | DOAJ |
| description | Abstract Hepatocellular carcinoma (HCC) is a widely prevalent type of primary liver cancer. However, strategies for pretumor intervention are still limited. In this study, a liver‐specific Zbtb7b knockout mouse model was used to evaluate the role of Zbtb7b in metabolic dysfunction‐associated steatotic liver disease (MASLD)‐related HCC development. We revealed that Zbtb7b was compensatively increased and restricted lipid deposition in the liver during MASLD progression, which protects against MASLD‐related HCC initiation. Mechanistically, Zbtb7b suppresses the expression of the long noncoding RNA H19 to attenuate hepatic de novo lipogenesis and increase fatty acid oxidation, thereby preventing lipid accumulation in hepatocytes. As a result, the proliferation and migration abilities of HCC cells are reduced. Overall, we demonstrated that Zbtb7b serves as a tumor suppressor at an early stage of HCC, thus providing a promising target for the treatment of HCC at a premalignant stage. |
| format | Article |
| id | doaj-art-9d3196648a8b4f0b9bfca5c300b7ad74 |
| institution | Kabale University |
| issn | 2051-817X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj-art-9d3196648a8b4f0b9bfca5c300b7ad742024-12-31T08:52:31ZengWileyPhysiological Reports2051-817X2024-12-011224n/an/a10.14814/phy2.70160Zbtb7b defines a compensatory mechanism in MASLD‐related HCC progression by suppressing H19‐mediated hepatic lipid depositionYinglin Han0Kaimin Wu1Xin Peng2Yinkun Fu3Wenyan Li4Jing Ma5He Jiang6Xu‐Yun Zhao7Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Endocrinology and Metabolism, Renji Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaLiver Cancer Institute, Zhongshan Hospital Fudan University, Shanghai Medical College Shanghai ChinaDepartment of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education Shanghai Jiao Tong University School of Medicine Shanghai ChinaAbstract Hepatocellular carcinoma (HCC) is a widely prevalent type of primary liver cancer. However, strategies for pretumor intervention are still limited. In this study, a liver‐specific Zbtb7b knockout mouse model was used to evaluate the role of Zbtb7b in metabolic dysfunction‐associated steatotic liver disease (MASLD)‐related HCC development. We revealed that Zbtb7b was compensatively increased and restricted lipid deposition in the liver during MASLD progression, which protects against MASLD‐related HCC initiation. Mechanistically, Zbtb7b suppresses the expression of the long noncoding RNA H19 to attenuate hepatic de novo lipogenesis and increase fatty acid oxidation, thereby preventing lipid accumulation in hepatocytes. As a result, the proliferation and migration abilities of HCC cells are reduced. Overall, we demonstrated that Zbtb7b serves as a tumor suppressor at an early stage of HCC, thus providing a promising target for the treatment of HCC at a premalignant stage.https://doi.org/10.14814/phy2.70160de novo lipogenesisfatty acid oxidationH19hepatocellular carcinomametabolic dysfunction‐associated steatotic liver diseaseZbtb7b |
| spellingShingle | Yinglin Han Kaimin Wu Xin Peng Yinkun Fu Wenyan Li Jing Ma He Jiang Xu‐Yun Zhao Zbtb7b defines a compensatory mechanism in MASLD‐related HCC progression by suppressing H19‐mediated hepatic lipid deposition Physiological Reports de novo lipogenesis fatty acid oxidation H19 hepatocellular carcinoma metabolic dysfunction‐associated steatotic liver disease Zbtb7b |
| title | Zbtb7b defines a compensatory mechanism in MASLD‐related HCC progression by suppressing H19‐mediated hepatic lipid deposition |
| title_full | Zbtb7b defines a compensatory mechanism in MASLD‐related HCC progression by suppressing H19‐mediated hepatic lipid deposition |
| title_fullStr | Zbtb7b defines a compensatory mechanism in MASLD‐related HCC progression by suppressing H19‐mediated hepatic lipid deposition |
| title_full_unstemmed | Zbtb7b defines a compensatory mechanism in MASLD‐related HCC progression by suppressing H19‐mediated hepatic lipid deposition |
| title_short | Zbtb7b defines a compensatory mechanism in MASLD‐related HCC progression by suppressing H19‐mediated hepatic lipid deposition |
| title_sort | zbtb7b defines a compensatory mechanism in masld related hcc progression by suppressing h19 mediated hepatic lipid deposition |
| topic | de novo lipogenesis fatty acid oxidation H19 hepatocellular carcinoma metabolic dysfunction‐associated steatotic liver disease Zbtb7b |
| url | https://doi.org/10.14814/phy2.70160 |
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