Tripartite motif-containing 14 (TRIM14) promotes epithelial-mesenchymal transition via ZEB2 in glioblastoma cells
Abstract Background Several members of the tripartite motif-containing (TRIM) protein family have been reported to serve as vital regulators of tumorigenesis. Recent studies have demonstrated an oncogenic role of TRIM 14 in multiple human cancers; however, the importance of this protein in glioblast...
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doaj-74071be4e85346adaf5e4e43bf980d392020-11-24T21:42:11ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662019-02-0138111310.1186/s13046-019-1070-xTripartite motif-containing 14 (TRIM14) promotes epithelial-mesenchymal transition via ZEB2 in glioblastoma cellsShuang Feng0Xiaomin Cai1Yangyang Li2Xiaoguang Jian3Linxin Zhang4Bin Li5Department of Encephalopathy, The Third Affiliated Hospital of Nanjing University of Chinese MedicineDepartment of Neurosurgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Encephalopathy, The Third Affiliated Hospital of Nanjing University of Chinese MedicineDepartment of Encephalopathy, The Third Affiliated Hospital of Nanjing University of Chinese MedicineDepartment of Encephalopathy, The Third Affiliated Hospital of Nanjing University of Chinese MedicineAbstract Background Several members of the tripartite motif-containing (TRIM) protein family have been reported to serve as vital regulators of tumorigenesis. Recent studies have demonstrated an oncogenic role of TRIM 14 in multiple human cancers; however, the importance of this protein in glioblastoma remains to be elucidated. Methods The expression levels of TRIM14 were analyzed in a series of database and were examined in a variety of glioblastoma cell lines. Two independent TRIM14 shRNA were transfected into LN229 and U251 cells, and the effect of TRIM14 depletion was confirmed. Transwell assay and wound healing assay assay were carried out to assess the effect of TRIM14 depletion on glioblastoma cell invasion and migration. Western blotting was performed to screen the downstream gene of TRIM14. The stability analysis and Ubiquitylation assays and Orthotopic xenograft studies were also performed to investigate the role of TRIM14 and the relationship with downstream gene. Human glioblastoma tissues were obtained and immunohistochemical staining were carried out to confirm the clinical significance of TRIM14. Results In this study, we showed that TRIM14 was upregulated in human glioblastoma specimens and cell lines, and correlated with glioblastoma progression and shorter patient survival times. Functional experiments showed that decreased TRIM14 expression reduced glioblastoma cell invasion and migration. Furthermore, we identified that zinc finger E-box binding homeobox 2 (ZEB2), a transcription factor involved in epithelial–mesenchymal transition, is a downstream target of TRIM14. Further investigation revealed that TRIM14 inactivation significantly facilitated ZEB2 ubiquitination and proteasomal degradation, which led to aggressive invasion and migration. Our findings provide insight into the specific biological role of TRIM14 in tumor invasion. Conclusions Our findings provide insight into the specific biological role of TRIM14 in tumor invasion, and suggest that targeting the TRIM14/ZEB2 axis might be a novel therapeutic approach for blocking glioblastoma.http://link.springer.com/article/10.1186/s13046-019-1070-xGlioblastomaTRIM14ZEB2InvasionUbiquitination |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shuang Feng Xiaomin Cai Yangyang Li Xiaoguang Jian Linxin Zhang Bin Li |
spellingShingle |
Shuang Feng Xiaomin Cai Yangyang Li Xiaoguang Jian Linxin Zhang Bin Li Tripartite motif-containing 14 (TRIM14) promotes epithelial-mesenchymal transition via ZEB2 in glioblastoma cells Journal of Experimental & Clinical Cancer Research Glioblastoma TRIM14 ZEB2 Invasion Ubiquitination |
author_facet |
Shuang Feng Xiaomin Cai Yangyang Li Xiaoguang Jian Linxin Zhang Bin Li |
author_sort |
Shuang Feng |
title |
Tripartite motif-containing 14 (TRIM14) promotes epithelial-mesenchymal transition via ZEB2 in glioblastoma cells |
title_short |
Tripartite motif-containing 14 (TRIM14) promotes epithelial-mesenchymal transition via ZEB2 in glioblastoma cells |
title_full |
Tripartite motif-containing 14 (TRIM14) promotes epithelial-mesenchymal transition via ZEB2 in glioblastoma cells |
title_fullStr |
Tripartite motif-containing 14 (TRIM14) promotes epithelial-mesenchymal transition via ZEB2 in glioblastoma cells |
title_full_unstemmed |
Tripartite motif-containing 14 (TRIM14) promotes epithelial-mesenchymal transition via ZEB2 in glioblastoma cells |
title_sort |
tripartite motif-containing 14 (trim14) promotes epithelial-mesenchymal transition via zeb2 in glioblastoma cells |
publisher |
BMC |
series |
Journal of Experimental & Clinical Cancer Research |
issn |
1756-9966 |
publishDate |
2019-02-01 |
description |
Abstract Background Several members of the tripartite motif-containing (TRIM) protein family have been reported to serve as vital regulators of tumorigenesis. Recent studies have demonstrated an oncogenic role of TRIM 14 in multiple human cancers; however, the importance of this protein in glioblastoma remains to be elucidated. Methods The expression levels of TRIM14 were analyzed in a series of database and were examined in a variety of glioblastoma cell lines. Two independent TRIM14 shRNA were transfected into LN229 and U251 cells, and the effect of TRIM14 depletion was confirmed. Transwell assay and wound healing assay assay were carried out to assess the effect of TRIM14 depletion on glioblastoma cell invasion and migration. Western blotting was performed to screen the downstream gene of TRIM14. The stability analysis and Ubiquitylation assays and Orthotopic xenograft studies were also performed to investigate the role of TRIM14 and the relationship with downstream gene. Human glioblastoma tissues were obtained and immunohistochemical staining were carried out to confirm the clinical significance of TRIM14. Results In this study, we showed that TRIM14 was upregulated in human glioblastoma specimens and cell lines, and correlated with glioblastoma progression and shorter patient survival times. Functional experiments showed that decreased TRIM14 expression reduced glioblastoma cell invasion and migration. Furthermore, we identified that zinc finger E-box binding homeobox 2 (ZEB2), a transcription factor involved in epithelial–mesenchymal transition, is a downstream target of TRIM14. Further investigation revealed that TRIM14 inactivation significantly facilitated ZEB2 ubiquitination and proteasomal degradation, which led to aggressive invasion and migration. Our findings provide insight into the specific biological role of TRIM14 in tumor invasion. Conclusions Our findings provide insight into the specific biological role of TRIM14 in tumor invasion, and suggest that targeting the TRIM14/ZEB2 axis might be a novel therapeutic approach for blocking glioblastoma. |
topic |
Glioblastoma TRIM14 ZEB2 Invasion Ubiquitination |
url |
http://link.springer.com/article/10.1186/s13046-019-1070-x |
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