E3 ubiquitin ligase RNF126 affects bladder cancer progression through regulation of PTEN stability
Abstract E3 ubiquitin ligase RNF126 (ring finger protein 126) is highly expressed in various cancers and strongly associated with tumorigenesis. However, its specific function in bladder cancer (BCa) is still debatable. Here, we found that RNF126 was significantly upregulated in BCa tissue by TCGA d...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2021-03-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-021-03521-1 |
| _version_ | 1818848123679670272 |
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| author | Huimin Xu Lingao Ju Yaoyi Xiong Mengxue Yu Fenfang Zhou Kaiyu Qian Gang Wang Yu Xiao Xinghuan Wang |
| author_facet | Huimin Xu Lingao Ju Yaoyi Xiong Mengxue Yu Fenfang Zhou Kaiyu Qian Gang Wang Yu Xiao Xinghuan Wang |
| author_sort | Huimin Xu |
| collection | DOAJ |
| description | Abstract E3 ubiquitin ligase RNF126 (ring finger protein 126) is highly expressed in various cancers and strongly associated with tumorigenesis. However, its specific function in bladder cancer (BCa) is still debatable. Here, we found that RNF126 was significantly upregulated in BCa tissue by TCGA database, and our studies indicated that downregulation of RNF126 significantly inhibited cell proliferation and metastasis through the EGFR/PI3K/AKT signaling pathway in BCa cells. Furthermore, we identified PTEN, an inhibitor of the PI3K/AKT signaling pathway, as a novel substrate for RNF126. By co-immunoprecipitation assays, we proved that RNF126 directly interacts with PTEN. Predominantly, PTEN binds to the C-terminal containing the RING domain of RNF126. The in vivo ubiquitination assay showed that RNF126 specifically regulates PTEN stability through poly-ubiquitination. Furthermore, PTEN knockdown restored cell proliferation, metastasis, and tumor formation of BCa cells inhibited by RNF126 silencing in vitro and in vivo. In conclusion, these results identified RNF126 as an oncogene that functions through ubiquitination and degradation of PTEN in BCa. |
| first_indexed | 2024-12-19T06:12:20Z |
| format | Article |
| id | doaj.art-4a47984ad7a1471895f2bb78bc5dd07c |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-19T06:12:20Z |
| publishDate | 2021-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-4a47984ad7a1471895f2bb78bc5dd07c2022-12-21T20:32:58ZengNature Publishing GroupCell Death and Disease2041-48892021-03-0112311410.1038/s41419-021-03521-1E3 ubiquitin ligase RNF126 affects bladder cancer progression through regulation of PTEN stabilityHuimin Xu0Lingao Ju1Yaoyi Xiong2Mengxue Yu3Fenfang Zhou4Kaiyu Qian5Gang Wang6Yu Xiao7Xinghuan Wang8Department of Urology, Zhongnan Hospital of Wuhan UniversityDepartment of Biological Repositories, Zhongnan Hospital of Wuhan UniversityDepartment of Urology, Zhongnan Hospital of Wuhan UniversityDepartment of Biological Repositories, Zhongnan Hospital of Wuhan UniversityDepartment of Urology, Zhongnan Hospital of Wuhan UniversityDepartment of Biological Repositories, Zhongnan Hospital of Wuhan UniversityDepartment of Biological Repositories, Zhongnan Hospital of Wuhan UniversityDepartment of Urology, Zhongnan Hospital of Wuhan UniversityDepartment of Urology, Zhongnan Hospital of Wuhan UniversityAbstract E3 ubiquitin ligase RNF126 (ring finger protein 126) is highly expressed in various cancers and strongly associated with tumorigenesis. However, its specific function in bladder cancer (BCa) is still debatable. Here, we found that RNF126 was significantly upregulated in BCa tissue by TCGA database, and our studies indicated that downregulation of RNF126 significantly inhibited cell proliferation and metastasis through the EGFR/PI3K/AKT signaling pathway in BCa cells. Furthermore, we identified PTEN, an inhibitor of the PI3K/AKT signaling pathway, as a novel substrate for RNF126. By co-immunoprecipitation assays, we proved that RNF126 directly interacts with PTEN. Predominantly, PTEN binds to the C-terminal containing the RING domain of RNF126. The in vivo ubiquitination assay showed that RNF126 specifically regulates PTEN stability through poly-ubiquitination. Furthermore, PTEN knockdown restored cell proliferation, metastasis, and tumor formation of BCa cells inhibited by RNF126 silencing in vitro and in vivo. In conclusion, these results identified RNF126 as an oncogene that functions through ubiquitination and degradation of PTEN in BCa.https://doi.org/10.1038/s41419-021-03521-1 |
| spellingShingle | Huimin Xu Lingao Ju Yaoyi Xiong Mengxue Yu Fenfang Zhou Kaiyu Qian Gang Wang Yu Xiao Xinghuan Wang E3 ubiquitin ligase RNF126 affects bladder cancer progression through regulation of PTEN stability Cell Death and Disease |
| title | E3 ubiquitin ligase RNF126 affects bladder cancer progression through regulation of PTEN stability |
| title_full | E3 ubiquitin ligase RNF126 affects bladder cancer progression through regulation of PTEN stability |
| title_fullStr | E3 ubiquitin ligase RNF126 affects bladder cancer progression through regulation of PTEN stability |
| title_full_unstemmed | E3 ubiquitin ligase RNF126 affects bladder cancer progression through regulation of PTEN stability |
| title_short | E3 ubiquitin ligase RNF126 affects bladder cancer progression through regulation of PTEN stability |
| title_sort | e3 ubiquitin ligase rnf126 affects bladder cancer progression through regulation of pten stability |
| url | https://doi.org/10.1038/s41419-021-03521-1 |
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