PRL1 Promotes Glioblastoma Invasion and Tumorigenesis via Activating USP36-Mediated Snail2 Deubiquitination
Regenerating liver phosphatase 1 (PRL1) is an established oncogene in various cancers, although its biological function and the underlying mechanisms in glioblastoma multiforme (GBM) remain unclear. Here, we showed that PRL1 was significantly upregulated in glioma tissues and cell lines, and positiv...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.795633/full |
| _version_ | 1819009804273713152 |
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| author | Wenjin Qiu Wenjin Qiu Xiaomin Cai Kaya Xu Shibin Song Zumu Xiao Yunan Hou Xiaolan Qi Feng Liu Yimin Chen Hua Yang Liangzhao Chu Jian Liu Jian Liu |
| author_facet | Wenjin Qiu Wenjin Qiu Xiaomin Cai Kaya Xu Shibin Song Zumu Xiao Yunan Hou Xiaolan Qi Feng Liu Yimin Chen Hua Yang Liangzhao Chu Jian Liu Jian Liu |
| author_sort | Wenjin Qiu |
| collection | DOAJ |
| description | Regenerating liver phosphatase 1 (PRL1) is an established oncogene in various cancers, although its biological function and the underlying mechanisms in glioblastoma multiforme (GBM) remain unclear. Here, we showed that PRL1 was significantly upregulated in glioma tissues and cell lines, and positively correlated with the tumor grade. Consistently, ectopic expression of PRL1 in glioma cell lines significantly enhanced their tumorigenicity and invasion both in vitro and in vivo by promoting epithelial-mesenchymal transition (EMT). Conversely, knocking down PRL1 blocked EMT in GBM cells, and inhibited their invasion, migration and tumorigenic growth. Additionally, PRL1 also stabilized Snail2 through its deubiquitination by activating USP36, thus revealing Snail2 as a crucial mediator of the oncogenic effects of PRL1 in GBM pathogenesis. Finally, PRL1 protein levels were positively correlated with that of Snail2 and predicted poor outcome of GBMs. Collectively, our data support that PRL1 promotes GBM progression by activating USP36-mediated Snail2 deubiquitination. This novel PRL1/USP36/Snail2 axis may be a promising therapeutic target for glioblastoma. |
| first_indexed | 2024-12-21T01:02:11Z |
| format | Article |
| id | doaj.art-25409aee6cfe45e2b784a1b04453287d |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-21T01:02:11Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-25409aee6cfe45e2b784a1b04453287d2022-12-21T19:21:09ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-01-011110.3389/fonc.2021.795633795633PRL1 Promotes Glioblastoma Invasion and Tumorigenesis via Activating USP36-Mediated Snail2 DeubiquitinationWenjin Qiu0Wenjin Qiu1Xiaomin Cai2Kaya Xu3Shibin Song4Zumu Xiao5Yunan Hou6Xiaolan Qi7Feng Liu8Yimin Chen9Hua Yang10Liangzhao Chu11Jian Liu12Jian Liu13Department of Neurosurgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, ChinaSchool of Basic Medical Sciences, Guizhou Medical University, Guiyang, ChinaDepartment of Neurosurgery, School of Medicine, Xinhua Hospital, Shanghai Jiaotong University, Shanghai, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, ChinaKey Laboratory of Endemic and Ethnic Diseases, Ministry of Education and Key Laboratory of Medical Molecular Biology of Guizhou Province, Guizhou Medical University, Guiyang, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, ChinaSchool of Basic Medical Sciences, Guizhou Medical University, Guiyang, ChinaDepartment of Neurosurgery, Guizhou Provincial People’s Hospital, Guiyang, ChinaRegenerating liver phosphatase 1 (PRL1) is an established oncogene in various cancers, although its biological function and the underlying mechanisms in glioblastoma multiforme (GBM) remain unclear. Here, we showed that PRL1 was significantly upregulated in glioma tissues and cell lines, and positively correlated with the tumor grade. Consistently, ectopic expression of PRL1 in glioma cell lines significantly enhanced their tumorigenicity and invasion both in vitro and in vivo by promoting epithelial-mesenchymal transition (EMT). Conversely, knocking down PRL1 blocked EMT in GBM cells, and inhibited their invasion, migration and tumorigenic growth. Additionally, PRL1 also stabilized Snail2 through its deubiquitination by activating USP36, thus revealing Snail2 as a crucial mediator of the oncogenic effects of PRL1 in GBM pathogenesis. Finally, PRL1 protein levels were positively correlated with that of Snail2 and predicted poor outcome of GBMs. Collectively, our data support that PRL1 promotes GBM progression by activating USP36-mediated Snail2 deubiquitination. This novel PRL1/USP36/Snail2 axis may be a promising therapeutic target for glioblastoma.https://www.frontiersin.org/articles/10.3389/fonc.2021.795633/fullglioblastomaPRL1epithelial mesenchymal transitionSnail2deubiquitination |
| spellingShingle | Wenjin Qiu Wenjin Qiu Xiaomin Cai Kaya Xu Shibin Song Zumu Xiao Yunan Hou Xiaolan Qi Feng Liu Yimin Chen Hua Yang Liangzhao Chu Jian Liu Jian Liu PRL1 Promotes Glioblastoma Invasion and Tumorigenesis via Activating USP36-Mediated Snail2 Deubiquitination Frontiers in Oncology glioblastoma PRL1 epithelial mesenchymal transition Snail2 deubiquitination |
| title | PRL1 Promotes Glioblastoma Invasion and Tumorigenesis via Activating USP36-Mediated Snail2 Deubiquitination |
| title_full | PRL1 Promotes Glioblastoma Invasion and Tumorigenesis via Activating USP36-Mediated Snail2 Deubiquitination |
| title_fullStr | PRL1 Promotes Glioblastoma Invasion and Tumorigenesis via Activating USP36-Mediated Snail2 Deubiquitination |
| title_full_unstemmed | PRL1 Promotes Glioblastoma Invasion and Tumorigenesis via Activating USP36-Mediated Snail2 Deubiquitination |
| title_short | PRL1 Promotes Glioblastoma Invasion and Tumorigenesis via Activating USP36-Mediated Snail2 Deubiquitination |
| title_sort | prl1 promotes glioblastoma invasion and tumorigenesis via activating usp36 mediated snail2 deubiquitination |
| topic | glioblastoma PRL1 epithelial mesenchymal transition Snail2 deubiquitination |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.795633/full |
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