RRC ID 54860
Author Feng S, Cai X, Li Y, Jian X, Zhang L, Li B.
Title Tripartite motif-containing 14 (TRIM14) promotes epithelial-mesenchymal transition via ZEB2 in glioblastoma cells.
Journal J Exp Clin Cancer Res
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.
Volume 38(1)
Pages 57
Published 2019-2-6
DOI 10.1186/s13046-019-1070-x
PII 10.1186/s13046-019-1070-x
PMID 30728039
PMC PMC6364431
MeSH Biomarkers, Tumor / metabolism Carcinogenesis / metabolism Carrier Proteins / biosynthesis Carrier Proteins / metabolism* Carrier Proteins / therapeutic use Cell Line, Tumor Cell Movement Central Nervous System Neoplasms / metabolism* Central Nervous System Neoplasms / pathology* Central Nervous System Neoplasms / therapy Cohort Studies Epithelial-Mesenchymal Transition* Glioblastoma / metabolism* Glioblastoma / pathology* Glioblastoma / therapy Humans Intracellular Signaling Peptides and Proteins Molecular Targeted Therapy Neoplasm Invasiveness Proteolysis Tripartite Motif Proteins Up-Regulation Zinc Finger E-box Binding Homeobox 2 / metabolism*
IF 5.646
Times Cited 9
Human and Animal Cells U251(RCB0461) T98G(RCB1954)