Isoacteoside alleviates hepatocellular carcinoma progression by inhibiting PDHB-mediated reprogramming of glucose metabolism
Abstract Pyruvate dehydrogenase B (PDHB) is an important component of the pyruvate dehydrogenase complex and is implicated in altering tumor metabolism and promoting malignancy. However, the specific impact of PDHB on hepatocellular carcinoma (HCC) metabolic reprogramming and its role in tumor progr...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07622-x |
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| author | Lijun Zhao Haonan Qi Weiting Liu Huiying Lv Peixian Li Wenyue Liu Ruili Sun Qiongzi Wang Xiangpeng Wang |
| author_facet | Lijun Zhao Haonan Qi Weiting Liu Huiying Lv Peixian Li Wenyue Liu Ruili Sun Qiongzi Wang Xiangpeng Wang |
| author_sort | Lijun Zhao |
| collection | DOAJ |
| description | Abstract Pyruvate dehydrogenase B (PDHB) is an important component of the pyruvate dehydrogenase complex and is implicated in altering tumor metabolism and promoting malignancy. However, the specific impact of PDHB on hepatocellular carcinoma (HCC) metabolic reprogramming and its role in tumor progression remain to be elucidated. In our investigation, we have discerned a pronounced elevation in PDHB expression within HCC, intricately linked to delayed tumor staging, heightened tumor grading, and diminished prognostic outcomes. PDHB overexpression drives tumor growth and metastasis in vitro and in vivo. Mechanistically, PDHB mediates metabolic reprogramming by binding to the promoter regions of SLC2A1, GPI, and PKM2, promoting glycolysis-related gene transcription, contributes to HCC sorafenib resistance. In addition, Isoacteoside is a targeted inhibitor of PDHB and exert antitumor effects on HCC. In the mouse xenograft model, the combination of isoacteoside and sorafenib shows significantly better effects than sorafenib alone. In summary, our study validates PDHB as an oncogenic drug resistance-related gene capable of predicting HCC tumor progression. PDHB and Isoacteoside could be potential avenues for targeted and combination therapies in liver cancer. |
| format | Article |
| id | doaj-art-2b095cb556b240ee9b4485b652f5aeea |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-2b095cb556b240ee9b4485b652f5aeea2025-02-09T12:50:19ZengNature PortfolioCommunications Biology2399-36422025-02-018111310.1038/s42003-025-07622-xIsoacteoside alleviates hepatocellular carcinoma progression by inhibiting PDHB-mediated reprogramming of glucose metabolismLijun Zhao0Haonan Qi1Weiting Liu2Huiying Lv3Peixian Li4Wenyue Liu5Ruili Sun6Qiongzi Wang7Xiangpeng Wang8Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Medical Technology, Xinxiang Medical UniversityHenan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Medical Technology, Xinxiang Medical UniversityHenan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Medical Technology, Xinxiang Medical UniversityHenan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Medical Technology, Xinxiang Medical UniversityHenan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Medical Technology, Xinxiang Medical UniversityHenan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Medical Technology, Xinxiang Medical UniversityHenan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Medical Technology, Xinxiang Medical UniversityHenan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Medical Technology, Xinxiang Medical UniversityHenan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Medical Technology, Xinxiang Medical UniversityAbstract Pyruvate dehydrogenase B (PDHB) is an important component of the pyruvate dehydrogenase complex and is implicated in altering tumor metabolism and promoting malignancy. However, the specific impact of PDHB on hepatocellular carcinoma (HCC) metabolic reprogramming and its role in tumor progression remain to be elucidated. In our investigation, we have discerned a pronounced elevation in PDHB expression within HCC, intricately linked to delayed tumor staging, heightened tumor grading, and diminished prognostic outcomes. PDHB overexpression drives tumor growth and metastasis in vitro and in vivo. Mechanistically, PDHB mediates metabolic reprogramming by binding to the promoter regions of SLC2A1, GPI, and PKM2, promoting glycolysis-related gene transcription, contributes to HCC sorafenib resistance. In addition, Isoacteoside is a targeted inhibitor of PDHB and exert antitumor effects on HCC. In the mouse xenograft model, the combination of isoacteoside and sorafenib shows significantly better effects than sorafenib alone. In summary, our study validates PDHB as an oncogenic drug resistance-related gene capable of predicting HCC tumor progression. PDHB and Isoacteoside could be potential avenues for targeted and combination therapies in liver cancer.https://doi.org/10.1038/s42003-025-07622-x |
| spellingShingle | Lijun Zhao Haonan Qi Weiting Liu Huiying Lv Peixian Li Wenyue Liu Ruili Sun Qiongzi Wang Xiangpeng Wang Isoacteoside alleviates hepatocellular carcinoma progression by inhibiting PDHB-mediated reprogramming of glucose metabolism Communications Biology |
| title | Isoacteoside alleviates hepatocellular carcinoma progression by inhibiting PDHB-mediated reprogramming of glucose metabolism |
| title_full | Isoacteoside alleviates hepatocellular carcinoma progression by inhibiting PDHB-mediated reprogramming of glucose metabolism |
| title_fullStr | Isoacteoside alleviates hepatocellular carcinoma progression by inhibiting PDHB-mediated reprogramming of glucose metabolism |
| title_full_unstemmed | Isoacteoside alleviates hepatocellular carcinoma progression by inhibiting PDHB-mediated reprogramming of glucose metabolism |
| title_short | Isoacteoside alleviates hepatocellular carcinoma progression by inhibiting PDHB-mediated reprogramming of glucose metabolism |
| title_sort | isoacteoside alleviates hepatocellular carcinoma progression by inhibiting pdhb mediated reprogramming of glucose metabolism |
| url | https://doi.org/10.1038/s42003-025-07622-x |
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