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TRIM37 interacts with EZH2 to epigenetically suppress PTCH1 and regulate stemness in glioma stem cells through sonic hedgehog pathway.
- Source :
-
Journal of neuro-oncology [J Neurooncol] 2024 Sep; Vol. 169 (2), pp. 269-279. Date of Electronic Publication: 2024 Jun 17. - Publication Year :
- 2024
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Abstract
- Background: Glioma stem cells (GSCs), which are known for their therapy resistance, play a substantial role in treatment inefficacy for glioblastoma multiforme (GBM). TRIM37, a member of the tripartite motif (TRIM) protein family initially linked to a rare growth disorder, has been recognized for its oncogenic role. However, the mechanism by which TRIM37 regulates tumor growth in glioma and GSCs is unclear.<br />Methods: For the in vitro experiments, gene expression was measured by western blotting, RT-qPCR, and immunofluorescence. Cell viability was detected by CCK-8, and cell apoptosis was detected by flow cytometry. The interaction between Enhancer of Zeste Homolog 2 (EZH2) and TRIM37 was verified by co-immunoprecipitation (Co-IP). The interaction between EZH2 and the PTCH1 promoter was verified using dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP). For the in vivo experiments, an orthotopically implanted glioma mouse model was used to validate tumor growth.<br />Results: The expression of TRIM37 is higher in GSCs compared with matched non-GSCs. TRIM37 knockdown promotes apoptosis, decreased stemness in GSCs, and reduces tumor growth in GSCs xenografts of nude mice. TRIM37 and EZH2 co-localize in the nucleus and interact with each other. TRIM37 knockdown or EZH2 inhibition downregulates the protein expressions associated with the Sonic Hedgehog (SHH) pathway. EZH2 epigenetically downregulates PTCH1 to activate SHH pathway in GSCs.<br />Conclusions: TRIM37 maintains the cell growth and stemness in GSCs through the interaction with EZH2. EZH2 activates SHH stem cell signaling pathway by downregulating the expression of SHH pathway suppressor PTCH1. Our findings suggest that TRIM37 may be a potential therapeutic target for GBM.<br /> (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Subjects :
- Humans
Animals
Mice
Mice, Nude
Epigenesis, Genetic
Gene Expression Regulation, Neoplastic
Apoptosis
Cell Line, Tumor
Cell Proliferation
Xenograft Model Antitumor Assays
Enhancer of Zeste Homolog 2 Protein metabolism
Enhancer of Zeste Homolog 2 Protein genetics
Patched-1 Receptor genetics
Patched-1 Receptor metabolism
Hedgehog Proteins metabolism
Hedgehog Proteins genetics
Neoplastic Stem Cells metabolism
Neoplastic Stem Cells pathology
Tripartite Motif Proteins genetics
Tripartite Motif Proteins metabolism
Glioma metabolism
Glioma genetics
Glioma pathology
Ubiquitin-Protein Ligases genetics
Ubiquitin-Protein Ligases metabolism
Signal Transduction
Brain Neoplasms genetics
Brain Neoplasms metabolism
Brain Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1573-7373
- Volume :
- 169
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of neuro-oncology
- Publication Type :
- Academic Journal
- Accession number :
- 38884661
- Full Text :
- https://doi.org/10.1007/s11060-024-04726-y