Overexpression of RNF38 facilitates TGF-β signaling by Ubiquitinating and degrading AHNAK in hepatocellular carcinoma
Abstract Background RING finger protein 38 (RNF38), a member of the RNF protein family, has just emerged as a vital driver of cancer progression. However, the oncogenic mechanisms of RNF38 remain unexplored. Methods Using frozen tumor tissue and tissue microarray from hepatocellular carcinoma (HCC)...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-03-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-019-1113-3 |
| _version_ | 1818217938981748736 |
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| author | Rui Peng Peng-Fei Zhang Xuan Yang Chuan-Yuan Wei Xiao-Yong Huang Jia-Bin Cai Jia-Cheng Lu Chao Gao Hai-Xiang Sun Qiang Gao Dou-Sheng Bai Guo-Ming Shi Ai-Wu Ke Jia Fan |
| author_facet | Rui Peng Peng-Fei Zhang Xuan Yang Chuan-Yuan Wei Xiao-Yong Huang Jia-Bin Cai Jia-Cheng Lu Chao Gao Hai-Xiang Sun Qiang Gao Dou-Sheng Bai Guo-Ming Shi Ai-Wu Ke Jia Fan |
| author_sort | Rui Peng |
| collection | DOAJ |
| description | Abstract Background RING finger protein 38 (RNF38), a member of the RNF protein family, has just emerged as a vital driver of cancer progression. However, the oncogenic mechanisms of RNF38 remain unexplored. Methods Using frozen tumor tissue and tissue microarray from hepatocellular carcinoma (HCC) patients, we tried to probe the expression of RNF38 in HCC and its clinical value. Then the biological functions of RNF38 were analyzed in vivo and vitro. Stable isotope labeling with amino acids (SILAC) in cell culture and co-immunoprecipitation proteomic analyses were combined to reveal the potential mechanism of RNF38 in HCC progression. Results We report that RNF38 expression was markedly higher in HCC tissues than in peritumor tissues. Correspondingly, RNF38 overexpression promoted the HCC cell migration and invasion and inhibited apoptosis both in vitro and in vivo. And elevated RNF38 expression induced HCC cell epithelial-mesenchymal transition by facilitating transforming growth factor-β (TGF-β) signaling via ubiquitinating and degrading neuroblast differentiation-associated protein (AHNAK), a well-established inhibitor of TGF-β signaling. Furthermore, AHNAK interference restored the HCC cell invasion and metastasis deprived by RNF38 downregulation. Clinically, elevated RNF38 and transforming growth factor beta receptor 1 (TGFBR1) expression was related to short overall survival (OS) and high cumulative recurrence rates in HCC patients. Conclusions High levels of RNF38 promote HCC by facilitating TGF-β signaling and are a novel marker for predicting the prognosis of HCC patients and a potential therapeutic target in HCC. |
| first_indexed | 2024-12-12T07:15:50Z |
| format | Article |
| id | doaj.art-2bdf0fd58bac47ceb3d853a69ef950ff |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-12T07:15:50Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-2bdf0fd58bac47ceb3d853a69ef950ff2022-12-22T00:33:31ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662019-03-0138111410.1186/s13046-019-1113-3Overexpression of RNF38 facilitates TGF-β signaling by Ubiquitinating and degrading AHNAK in hepatocellular carcinomaRui Peng0Peng-Fei Zhang1Xuan Yang2Chuan-Yuan Wei3Xiao-Yong Huang4Jia-Bin Cai5Jia-Cheng Lu6Chao Gao7Hai-Xiang Sun8Qiang Gao9Dou-Sheng Bai10Guo-Ming Shi11Ai-Wu Ke12Jia Fan13Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of EducationLiver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of EducationLiver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of EducationLiver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of EducationLiver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of EducationLiver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of EducationLiver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of EducationLiver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of EducationLiver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of EducationLiver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of EducationClinical Medical College, Yangzhou UniversityLiver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of EducationLiver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of EducationLiver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of EducationAbstract Background RING finger protein 38 (RNF38), a member of the RNF protein family, has just emerged as a vital driver of cancer progression. However, the oncogenic mechanisms of RNF38 remain unexplored. Methods Using frozen tumor tissue and tissue microarray from hepatocellular carcinoma (HCC) patients, we tried to probe the expression of RNF38 in HCC and its clinical value. Then the biological functions of RNF38 were analyzed in vivo and vitro. Stable isotope labeling with amino acids (SILAC) in cell culture and co-immunoprecipitation proteomic analyses were combined to reveal the potential mechanism of RNF38 in HCC progression. Results We report that RNF38 expression was markedly higher in HCC tissues than in peritumor tissues. Correspondingly, RNF38 overexpression promoted the HCC cell migration and invasion and inhibited apoptosis both in vitro and in vivo. And elevated RNF38 expression induced HCC cell epithelial-mesenchymal transition by facilitating transforming growth factor-β (TGF-β) signaling via ubiquitinating and degrading neuroblast differentiation-associated protein (AHNAK), a well-established inhibitor of TGF-β signaling. Furthermore, AHNAK interference restored the HCC cell invasion and metastasis deprived by RNF38 downregulation. Clinically, elevated RNF38 and transforming growth factor beta receptor 1 (TGFBR1) expression was related to short overall survival (OS) and high cumulative recurrence rates in HCC patients. Conclusions High levels of RNF38 promote HCC by facilitating TGF-β signaling and are a novel marker for predicting the prognosis of HCC patients and a potential therapeutic target in HCC.http://link.springer.com/article/10.1186/s13046-019-1113-3Hepatocellular carcinomaRNF38AHNAKTGF-β signalingPrognosis |
| spellingShingle | Rui Peng Peng-Fei Zhang Xuan Yang Chuan-Yuan Wei Xiao-Yong Huang Jia-Bin Cai Jia-Cheng Lu Chao Gao Hai-Xiang Sun Qiang Gao Dou-Sheng Bai Guo-Ming Shi Ai-Wu Ke Jia Fan Overexpression of RNF38 facilitates TGF-β signaling by Ubiquitinating and degrading AHNAK in hepatocellular carcinoma Journal of Experimental & Clinical Cancer Research Hepatocellular carcinoma RNF38 AHNAK TGF-β signaling Prognosis |
| title | Overexpression of RNF38 facilitates TGF-β signaling by Ubiquitinating and degrading AHNAK in hepatocellular carcinoma |
| title_full | Overexpression of RNF38 facilitates TGF-β signaling by Ubiquitinating and degrading AHNAK in hepatocellular carcinoma |
| title_fullStr | Overexpression of RNF38 facilitates TGF-β signaling by Ubiquitinating and degrading AHNAK in hepatocellular carcinoma |
| title_full_unstemmed | Overexpression of RNF38 facilitates TGF-β signaling by Ubiquitinating and degrading AHNAK in hepatocellular carcinoma |
| title_short | Overexpression of RNF38 facilitates TGF-β signaling by Ubiquitinating and degrading AHNAK in hepatocellular carcinoma |
| title_sort | overexpression of rnf38 facilitates tgf β signaling by ubiquitinating and degrading ahnak in hepatocellular carcinoma |
| topic | Hepatocellular carcinoma RNF38 AHNAK TGF-β signaling Prognosis |
| url | http://link.springer.com/article/10.1186/s13046-019-1113-3 |
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