RNF149 Promotes HCC Progression through Its E3 Ubiquitin Ligase Activity
Hepatocellular carcinoma (HCC) accounts for over 80% of cases among liver cancer, with high incidence and poor prognosis. Thus, it is of valuable clinical significance for discovery of potential biomarkers and drug targets for HCC. In this study, based on the proteomic profiling data of paired early...
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MDPI AG
2023-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/21/5203 |
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| author | Zhaoyu Guo Pei Jiang Qian Dong Yiming Zhang Kaikun Xu Yuanjun Zhai Fuchu He Chunyan Tian Aihua Sun |
| author_facet | Zhaoyu Guo Pei Jiang Qian Dong Yiming Zhang Kaikun Xu Yuanjun Zhai Fuchu He Chunyan Tian Aihua Sun |
| author_sort | Zhaoyu Guo |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) accounts for over 80% of cases among liver cancer, with high incidence and poor prognosis. Thus, it is of valuable clinical significance for discovery of potential biomarkers and drug targets for HCC. In this study, based on the proteomic profiling data of paired early-stage HCC samples, we found that RNF149 was strikingly upregulated in tumor tissues and correlated with poor prognosis in HCC patients, which was further validated by IHC staining experiments of an independent HCC cohort. Consistently, overexpression of RNF149 significantly promoted cell proliferation, migration, and invasion of HCC cells. We further proved that RNF149 stimulated HCC progression via its E3 ubiquitin ligase activity, and identified DNAJC25 as its new substrate. In addition, bioinformatics analysis showed that high expression of RNF149 was correlated with immunosuppressive tumor microenvironment (TME), indicating its potential role in immune regulation of HCC. These results suggest that RNF149 could exert protumor functions in HCC in dependence of its E3 ubiquitin ligase activity, and might be a potential prognostic marker and therapeutic target for HCC treatment. |
| first_indexed | 2024-03-11T11:32:14Z |
| format | Article |
| id | doaj.art-00a47774dcec4c0fb089887b6a02c98e |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T11:32:14Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-00a47774dcec4c0fb089887b6a02c98e2023-11-10T15:00:13ZengMDPI AGCancers2072-66942023-10-011521520310.3390/cancers15215203RNF149 Promotes HCC Progression through Its E3 Ubiquitin Ligase ActivityZhaoyu Guo0Pei Jiang1Qian Dong2Yiming Zhang3Kaikun Xu4Yuanjun Zhai5Fuchu He6Chunyan Tian7Aihua Sun8State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, ChinaState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, ChinaState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, ChinaState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, ChinaState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, ChinaState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, ChinaState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, ChinaState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, ChinaState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, ChinaHepatocellular carcinoma (HCC) accounts for over 80% of cases among liver cancer, with high incidence and poor prognosis. Thus, it is of valuable clinical significance for discovery of potential biomarkers and drug targets for HCC. In this study, based on the proteomic profiling data of paired early-stage HCC samples, we found that RNF149 was strikingly upregulated in tumor tissues and correlated with poor prognosis in HCC patients, which was further validated by IHC staining experiments of an independent HCC cohort. Consistently, overexpression of RNF149 significantly promoted cell proliferation, migration, and invasion of HCC cells. We further proved that RNF149 stimulated HCC progression via its E3 ubiquitin ligase activity, and identified DNAJC25 as its new substrate. In addition, bioinformatics analysis showed that high expression of RNF149 was correlated with immunosuppressive tumor microenvironment (TME), indicating its potential role in immune regulation of HCC. These results suggest that RNF149 could exert protumor functions in HCC in dependence of its E3 ubiquitin ligase activity, and might be a potential prognostic marker and therapeutic target for HCC treatment.https://www.mdpi.com/2072-6694/15/21/5203hepatocellular carcinoma (HCC)RNF149DNAJC25ubiquitinationtumor microenvironment (TME) |
| spellingShingle | Zhaoyu Guo Pei Jiang Qian Dong Yiming Zhang Kaikun Xu Yuanjun Zhai Fuchu He Chunyan Tian Aihua Sun RNF149 Promotes HCC Progression through Its E3 Ubiquitin Ligase Activity Cancers hepatocellular carcinoma (HCC) RNF149 DNAJC25 ubiquitination tumor microenvironment (TME) |
| title | RNF149 Promotes HCC Progression through Its E3 Ubiquitin Ligase Activity |
| title_full | RNF149 Promotes HCC Progression through Its E3 Ubiquitin Ligase Activity |
| title_fullStr | RNF149 Promotes HCC Progression through Its E3 Ubiquitin Ligase Activity |
| title_full_unstemmed | RNF149 Promotes HCC Progression through Its E3 Ubiquitin Ligase Activity |
| title_short | RNF149 Promotes HCC Progression through Its E3 Ubiquitin Ligase Activity |
| title_sort | rnf149 promotes hcc progression through its e3 ubiquitin ligase activity |
| topic | hepatocellular carcinoma (HCC) RNF149 DNAJC25 ubiquitination tumor microenvironment (TME) |
| url | https://www.mdpi.com/2072-6694/15/21/5203 |
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