NUF2 regulated the progression of hepatocellular carcinoma through modulating the PI3K/AKT pathway via stabilizing ERBB3
Hepatocellular carcinoma (HCC) is among the most prevalent and lethal cancers worldwide. The NDC80 kinetochore complex component NUF2 has been previously identified as up-regulating in HCC and associated with patient prognosis. However, the pathophysiological effects and molecular mechanisms of NUF2...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-06-01
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| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523324000603 |
| _version_ | 1797253951608848384 |
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| author | Yiwei Liu Yuming Wang Jifei Wang Wangjie Jiang Yananlan Chen Jijun Shan Xiao Li Xiaofeng Wu |
| author_facet | Yiwei Liu Yuming Wang Jifei Wang Wangjie Jiang Yananlan Chen Jijun Shan Xiao Li Xiaofeng Wu |
| author_sort | Yiwei Liu |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is among the most prevalent and lethal cancers worldwide. The NDC80 kinetochore complex component NUF2 has been previously identified as up-regulating in HCC and associated with patient prognosis. However, the pathophysiological effects and molecular mechanisms of NUF2 in tumorigenesis remain unclear. In this study, we confirmed a significant increase in NUF2 expression in HCC tissues and established a correlation between high NUF2 expression and adverse outcomes in HCC patients. Through in vitro and in vivo experiments, we demonstrated that genetic inhibition of NUF2 suppressed the proliferation of HCC cells and disrupted the cell cycle. Further investigation into the molecular mechanisms revealed that NUF2 interacted with ERBB3, inhibiting its ubiquitination degradation, thus activating the PI3K/AKT signaling pathway and influencing cell cycle regulation. Overall, this study revealed the crucial role of NUF2 in promoting the malignant progression of HCC, suggesting its potential as both a prognostic biomarker and a therapeutic target for HCC. |
| first_indexed | 2024-04-24T21:42:13Z |
| format | Article |
| id | doaj.art-0bde83ca00084d39ad1903527f62fc73 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-04-24T21:42:13Z |
| publishDate | 2024-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-0bde83ca00084d39ad1903527f62fc732024-03-21T05:36:12ZengElsevierTranslational Oncology1936-52332024-06-0144101933NUF2 regulated the progression of hepatocellular carcinoma through modulating the PI3K/AKT pathway via stabilizing ERBB3Yiwei Liu0Yuming Wang1Jifei Wang2Wangjie Jiang3Yananlan Chen4Jijun Shan5Xiao Li6Xiaofeng Wu7Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China; Jiangsu Provincial Medical Innovation Center; Jiangsu Provincial Medical Key Laboratory, Nanjing, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China; Jiangsu Provincial Medical Innovation Center; Jiangsu Provincial Medical Key Laboratory, Nanjing, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China; Jiangsu Provincial Medical Innovation Center; Jiangsu Provincial Medical Key Laboratory, Nanjing, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China; Jiangsu Provincial Medical Innovation Center; Jiangsu Provincial Medical Key Laboratory, Nanjing, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China; Jiangsu Provincial Medical Innovation Center; Jiangsu Provincial Medical Key Laboratory, Nanjing, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China; Jiangsu Provincial Medical Innovation Center; Jiangsu Provincial Medical Key Laboratory, Nanjing, ChinaDepartment of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Corresponding authors at: 300 Guangzhou Road, Nanjing, China.Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China; Jiangsu Provincial Medical Innovation Center; Jiangsu Provincial Medical Key Laboratory, Nanjing, China; Corresponding authors at: 300 Guangzhou Road, Nanjing, China.Hepatocellular carcinoma (HCC) is among the most prevalent and lethal cancers worldwide. The NDC80 kinetochore complex component NUF2 has been previously identified as up-regulating in HCC and associated with patient prognosis. However, the pathophysiological effects and molecular mechanisms of NUF2 in tumorigenesis remain unclear. In this study, we confirmed a significant increase in NUF2 expression in HCC tissues and established a correlation between high NUF2 expression and adverse outcomes in HCC patients. Through in vitro and in vivo experiments, we demonstrated that genetic inhibition of NUF2 suppressed the proliferation of HCC cells and disrupted the cell cycle. Further investigation into the molecular mechanisms revealed that NUF2 interacted with ERBB3, inhibiting its ubiquitination degradation, thus activating the PI3K/AKT signaling pathway and influencing cell cycle regulation. Overall, this study revealed the crucial role of NUF2 in promoting the malignant progression of HCC, suggesting its potential as both a prognostic biomarker and a therapeutic target for HCC.http://www.sciencedirect.com/science/article/pii/S1936523324000603HCCUbiquitinationNUF2ERBB3PI3K/AKT |
| spellingShingle | Yiwei Liu Yuming Wang Jifei Wang Wangjie Jiang Yananlan Chen Jijun Shan Xiao Li Xiaofeng Wu NUF2 regulated the progression of hepatocellular carcinoma through modulating the PI3K/AKT pathway via stabilizing ERBB3 Translational Oncology HCC Ubiquitination NUF2 ERBB3 PI3K/AKT |
| title | NUF2 regulated the progression of hepatocellular carcinoma through modulating the PI3K/AKT pathway via stabilizing ERBB3 |
| title_full | NUF2 regulated the progression of hepatocellular carcinoma through modulating the PI3K/AKT pathway via stabilizing ERBB3 |
| title_fullStr | NUF2 regulated the progression of hepatocellular carcinoma through modulating the PI3K/AKT pathway via stabilizing ERBB3 |
| title_full_unstemmed | NUF2 regulated the progression of hepatocellular carcinoma through modulating the PI3K/AKT pathway via stabilizing ERBB3 |
| title_short | NUF2 regulated the progression of hepatocellular carcinoma through modulating the PI3K/AKT pathway via stabilizing ERBB3 |
| title_sort | nuf2 regulated the progression of hepatocellular carcinoma through modulating the pi3k akt pathway via stabilizing erbb3 |
| topic | HCC Ubiquitination NUF2 ERBB3 PI3K/AKT |
| url | http://www.sciencedirect.com/science/article/pii/S1936523324000603 |
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