UCHL3 promotes hepatocellular carcinoma cell migration by de-ubiquitinating and stabilizing Vimentin
BackgroundHepatocellular carcinoma (HCC) is a common malignant tumor associated with a poor prognosis. Ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) has been reported to promote diverse tumors, but little is known about its role in HCC.MethodsExpression levels of UCHL3 in Huh7 and Hep3B cells wer...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1088475/full |
| _version_ | 1811157748909342720 |
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| author | Qiancheng Ma Qiancheng Ma Qiliang Lu Xiangxiang Lei Jie Zhao Wen Sun Jun Wang Qing Zhu Dongsheng Huang |
| author_facet | Qiancheng Ma Qiancheng Ma Qiliang Lu Xiangxiang Lei Jie Zhao Wen Sun Jun Wang Qing Zhu Dongsheng Huang |
| author_sort | Qiancheng Ma |
| collection | DOAJ |
| description | BackgroundHepatocellular carcinoma (HCC) is a common malignant tumor associated with a poor prognosis. Ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) has been reported to promote diverse tumors, but little is known about its role in HCC.MethodsExpression levels of UCHL3 in Huh7 and Hep3B cells were measured by qRT-PCR. UCHL3, Vimentin protein levels, and ubiquitination levels were determined by Western blot assay. co-immunoprecipitation, Immunofluorescence, and IHC were used to detect the interaction and expression association between UCHL3 and Vimentin in the cells. Wound healing and Transwell assays were used to measure cell migration. Spheroid formation assay were used to assess stem-like properties.ResultsUCHL3 expression was found to be significantly elevated in HCC and associated with poor prognosis. UCHL3 promoted migration and stem-like properties of HCC cells. Vimentin was identified as a potential de-ubiquitination substrate of UCHL3 and UCHL3 interacted with and promoted the de-ubiquitination of Vimentin, enhancing its stability. Moreover, the suppression of UCHL3 by siRNA or the inhibition by TCID upregulated ubiquitinated Vimentin. Vimentin attenuated the suppression of cell migration caused by knockdown of UCHL3.ConclusionUCHL3 was highly expressed in HCC and functioned as an oncogene. Vimentin is a novel substrate of UCHL3 and its stabilization and de-ubiquitination enhanced HCC cell migration. |
| first_indexed | 2024-04-10T05:12:34Z |
| format | Article |
| id | doaj.art-4e7a5b80ef3949e5865716cb00c69a97 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-10T05:12:34Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-4e7a5b80ef3949e5865716cb00c69a972023-03-09T07:00:55ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-03-011310.3389/fonc.2023.10884751088475UCHL3 promotes hepatocellular carcinoma cell migration by de-ubiquitinating and stabilizing VimentinQiancheng Ma0Qiancheng Ma1Qiliang Lu2Xiangxiang Lei3Jie Zhao4Wen Sun5Jun Wang6Qing Zhu7Dongsheng Huang8College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, ChinaThe Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, ChinaQingdao Medical College, Qingdao University, Qingdao, ChinaSchool of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, ChinaCollege of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, ChinaThe Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Emergency and Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaCollege of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, ChinaThe Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, ChinaBackgroundHepatocellular carcinoma (HCC) is a common malignant tumor associated with a poor prognosis. Ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) has been reported to promote diverse tumors, but little is known about its role in HCC.MethodsExpression levels of UCHL3 in Huh7 and Hep3B cells were measured by qRT-PCR. UCHL3, Vimentin protein levels, and ubiquitination levels were determined by Western blot assay. co-immunoprecipitation, Immunofluorescence, and IHC were used to detect the interaction and expression association between UCHL3 and Vimentin in the cells. Wound healing and Transwell assays were used to measure cell migration. Spheroid formation assay were used to assess stem-like properties.ResultsUCHL3 expression was found to be significantly elevated in HCC and associated with poor prognosis. UCHL3 promoted migration and stem-like properties of HCC cells. Vimentin was identified as a potential de-ubiquitination substrate of UCHL3 and UCHL3 interacted with and promoted the de-ubiquitination of Vimentin, enhancing its stability. Moreover, the suppression of UCHL3 by siRNA or the inhibition by TCID upregulated ubiquitinated Vimentin. Vimentin attenuated the suppression of cell migration caused by knockdown of UCHL3.ConclusionUCHL3 was highly expressed in HCC and functioned as an oncogene. Vimentin is a novel substrate of UCHL3 and its stabilization and de-ubiquitination enhanced HCC cell migration.https://www.frontiersin.org/articles/10.3389/fonc.2023.1088475/fullHCCUCHL3Vimentinde-ubiquitinationmigrationcancer stem cells |
| spellingShingle | Qiancheng Ma Qiancheng Ma Qiliang Lu Xiangxiang Lei Jie Zhao Wen Sun Jun Wang Qing Zhu Dongsheng Huang UCHL3 promotes hepatocellular carcinoma cell migration by de-ubiquitinating and stabilizing Vimentin Frontiers in Oncology HCC UCHL3 Vimentin de-ubiquitination migration cancer stem cells |
| title | UCHL3 promotes hepatocellular carcinoma cell migration by de-ubiquitinating and stabilizing Vimentin |
| title_full | UCHL3 promotes hepatocellular carcinoma cell migration by de-ubiquitinating and stabilizing Vimentin |
| title_fullStr | UCHL3 promotes hepatocellular carcinoma cell migration by de-ubiquitinating and stabilizing Vimentin |
| title_full_unstemmed | UCHL3 promotes hepatocellular carcinoma cell migration by de-ubiquitinating and stabilizing Vimentin |
| title_short | UCHL3 promotes hepatocellular carcinoma cell migration by de-ubiquitinating and stabilizing Vimentin |
| title_sort | uchl3 promotes hepatocellular carcinoma cell migration by de ubiquitinating and stabilizing vimentin |
| topic | HCC UCHL3 Vimentin de-ubiquitination migration cancer stem cells |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1088475/full |
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