Comprehensive analysis of protein post-translational modifications reveals PTPN2-STAT1-AOX axis-mediated tumor progression in hepatocellular carcinomas
Hepatocellular carcinoma (HCC) is a common malignant tumor. Although the proteomics of HCC is well studied, the landscape of post-translational modifications (PTMs) in HCC is poorly understood. The PTMs themselves and their crosstalk might be deeply involved in HCC development and progression. Herei...
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| Language: | English |
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Elsevier
2025-03-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523325000063 |
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| author | Junli Wang Yu Lou Xiaojun Peng Mao Ye Wanyue Cao Jiangchao Wu Zhihui Yan Xiaowen Zhao Yu Zhou Chenlei Zheng Xiaobao Wei Qitai Chen Chengyang Hu Mingxuan Zhang Lanqing Qu Zeshe Chen Qihan Fu Weixin Wang Jingsong Li Qi Zhang Tingbo Liang |
| author_facet | Junli Wang Yu Lou Xiaojun Peng Mao Ye Wanyue Cao Jiangchao Wu Zhihui Yan Xiaowen Zhao Yu Zhou Chenlei Zheng Xiaobao Wei Qitai Chen Chengyang Hu Mingxuan Zhang Lanqing Qu Zeshe Chen Qihan Fu Weixin Wang Jingsong Li Qi Zhang Tingbo Liang |
| author_sort | Junli Wang |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is a common malignant tumor. Although the proteomics of HCC is well studied, the landscape of post-translational modifications (PTMs) in HCC is poorly understood. The PTMs themselves and their crosstalk might be deeply involved in HCC development and progression. Herein, we investigated nine types of PTMs in paired tumor and normal tissues from nine patients with HCC using the label-free quantitative liquid chromatography with tandem mass spectrometry (LC-MS)-based technique. We identified >60,000 modified sites, and found that phosphorylation and ubiquitination were two most frequently changed PTMs between tumor and normal tissues. Crosstalk between malonylation-ubiquitination, phosphorylation-ubiquitination, and succinylation-propionylation were most significant among all PTMs. Further analysis revealed that Thr-160 of CDK2 regulated EZH2 via H3K27me3, and proposed a PTPN2-STAT1-AOX1 axis for HCC development through driver PTM exploration. In conclusion, our study provides a database of multiple PTMs in HCC, which might help to understand the biology of HCC and reveal novel targets for drug development. |
| format | Article |
| id | doaj-art-283f4fa854574b548b60a138c8d8d72f |
| institution | OA Journals |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-283f4fa854574b548b60a138c8d8d72f2025-08-20T02:03:46ZengElsevierTranslational Oncology1936-52332025-03-015310227510.1016/j.tranon.2025.102275Comprehensive analysis of protein post-translational modifications reveals PTPN2-STAT1-AOX axis-mediated tumor progression in hepatocellular carcinomasJunli Wang0Yu Lou1Xiaojun Peng2Mao Ye3Wanyue Cao4Jiangchao Wu5Zhihui Yan6Xiaowen Zhao7Yu Zhou8Chenlei Zheng9Xiaobao Wei10Qitai Chen11Chengyang Hu12Mingxuan Zhang13Lanqing Qu14Zeshe Chen15Qihan Fu16Weixin Wang17Jingsong Li18Qi Zhang19Tingbo Liang20Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaZhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaCosmos Wisdom Biotechnology Co. Ltd., Hangzhou, ChinaZhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaZhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaZhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaNovogene Inc., Beijing, ChinaNovogene Inc., Beijing, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaZhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaZhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaZhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaZhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaZhejiang University School of Medicine, Hangzhou, ChinaZhejiang University School of Medicine, Hangzhou, ChinaZhejiang University School of Medicine, Hangzhou, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Zhejiang Province, China; Department of Medical Oncology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaCosmos Wisdom Biotechnology Co. Ltd., Hangzhou, ChinaResearch Center for Healthcare Data Science, Zhejiang Lab, Hangzhou, ChinaZhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Zhejiang Province, China; Zhejiang University Cancer Center, Hangzhou, China; Corresponding author at: Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310003, China.Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Zhejiang Province, China; Zhejiang University Cancer Center, Hangzhou, China; Corresponding author at: Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310003, China.Hepatocellular carcinoma (HCC) is a common malignant tumor. Although the proteomics of HCC is well studied, the landscape of post-translational modifications (PTMs) in HCC is poorly understood. The PTMs themselves and their crosstalk might be deeply involved in HCC development and progression. Herein, we investigated nine types of PTMs in paired tumor and normal tissues from nine patients with HCC using the label-free quantitative liquid chromatography with tandem mass spectrometry (LC-MS)-based technique. We identified >60,000 modified sites, and found that phosphorylation and ubiquitination were two most frequently changed PTMs between tumor and normal tissues. Crosstalk between malonylation-ubiquitination, phosphorylation-ubiquitination, and succinylation-propionylation were most significant among all PTMs. Further analysis revealed that Thr-160 of CDK2 regulated EZH2 via H3K27me3, and proposed a PTPN2-STAT1-AOX1 axis for HCC development through driver PTM exploration. In conclusion, our study provides a database of multiple PTMs in HCC, which might help to understand the biology of HCC and reveal novel targets for drug development.http://www.sciencedirect.com/science/article/pii/S1936523325000063ProteomicPost-translational modificationHistoneCDK2Liver cancer |
| spellingShingle | Junli Wang Yu Lou Xiaojun Peng Mao Ye Wanyue Cao Jiangchao Wu Zhihui Yan Xiaowen Zhao Yu Zhou Chenlei Zheng Xiaobao Wei Qitai Chen Chengyang Hu Mingxuan Zhang Lanqing Qu Zeshe Chen Qihan Fu Weixin Wang Jingsong Li Qi Zhang Tingbo Liang Comprehensive analysis of protein post-translational modifications reveals PTPN2-STAT1-AOX axis-mediated tumor progression in hepatocellular carcinomas Translational Oncology Proteomic Post-translational modification Histone CDK2 Liver cancer |
| title | Comprehensive analysis of protein post-translational modifications reveals PTPN2-STAT1-AOX axis-mediated tumor progression in hepatocellular carcinomas |
| title_full | Comprehensive analysis of protein post-translational modifications reveals PTPN2-STAT1-AOX axis-mediated tumor progression in hepatocellular carcinomas |
| title_fullStr | Comprehensive analysis of protein post-translational modifications reveals PTPN2-STAT1-AOX axis-mediated tumor progression in hepatocellular carcinomas |
| title_full_unstemmed | Comprehensive analysis of protein post-translational modifications reveals PTPN2-STAT1-AOX axis-mediated tumor progression in hepatocellular carcinomas |
| title_short | Comprehensive analysis of protein post-translational modifications reveals PTPN2-STAT1-AOX axis-mediated tumor progression in hepatocellular carcinomas |
| title_sort | comprehensive analysis of protein post translational modifications reveals ptpn2 stat1 aox axis mediated tumor progression in hepatocellular carcinomas |
| topic | Proteomic Post-translational modification Histone CDK2 Liver cancer |
| url | http://www.sciencedirect.com/science/article/pii/S1936523325000063 |
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