Analysis and Functional Significance of TRAP1 in Glioblastoma
Introduction. Glioblastoma exhibits high aggressiveness and complex mechanisms of therapy resistance. Tumor necrosis factor receptor-associated protein 1 (TRAP1) participates in metabolic regulation and tumor cell resistance to apoptosis; however, its role in glioblastoma remains understudied. Mater...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Bashkir State Medical University
2025-07-01
|
| Series: | Креативная хирургия и онкология |
| Subjects: | |
| Online Access: | https://www.surgonco.ru/jour/article/view/1084 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849249681858625536 |
|---|---|
| author | I. F. Gareev O.A. Beylerli Zhang Hongli S. A. Roumiantsev |
| author_facet | I. F. Gareev O.A. Beylerli Zhang Hongli S. A. Roumiantsev |
| author_sort | I. F. Gareev |
| collection | DOAJ |
| description | Introduction. Glioblastoma exhibits high aggressiveness and complex mechanisms of therapy resistance. Tumor necrosis factor receptor-associated protein 1 (TRAP1) participates in metabolic regulation and tumor cell resistance to apoptosis; however, its role in glioblastoma remains understudied. Materials and methods. Glioma cell lines T98G and human brain astrocytes (HBA) were used as controls. TRAP1 expression was suppressed via the lentiviral transduction method using short hairpin RNA (shRNA). Exosomes were isolated from culture medium by ultracentrifugation and subsequently identified by typical markers (TSG101, CD63, and ALIX). The protein-level expression of TRAP1 and key glycolytic enzymes was analyzed by western blot analysis. Cell viability was assessed using the MTT assay, while apoptosis levels were measured using Annexin V-FITC/PI staining. In addition, ATP production was analyzed using bioluminescent methods. Results and discussion. TRAP1 was overexpressed in T98G cells, including in exosomes, while HBA exhibited moderate to low TRAP1 levels. The suppression of TRAP1 in T98G cells resulted in a decrease in glycolytic enzyme expression, an increase in apoptosis, and a decrease in cell viability. TRAP1 overexpression facilitated metabolic reprogramming toward aerobic glycolysis, along with reducing ATP synthesis. Exosomal TRAP1 likely participates in intercellular communication, promoting tumor adaptation to stress and the formation of a pro-tumor microenvironment. Conclusion. These findings support the pivotal role of TRAP1 in regulating metabolic status and maintaining aggressive phenotypes in glioblastoma. The targeted inhibition of TRAP1 may become a promising therapeutic strategy for glioblastoma, aimed at reducing tumor cell viability and limiting metabolic flexibility. |
| format | Article |
| id | doaj-art-9a092c1d00a64c8cb866d3748ab2138c |
| institution | Kabale University |
| issn | 2076-3093 2307-0501 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Bashkir State Medical University |
| record_format | Article |
| series | Креативная хирургия и онкология |
| spelling | doaj-art-9a092c1d00a64c8cb866d3748ab2138c2025-08-20T03:57:27ZengBashkir State Medical UniversityКреативная хирургия и онкология2076-30932307-05012025-07-0115211512310.24060/2076-3093-2025-15-2-19-27621Analysis and Functional Significance of TRAP1 in GlioblastomaI. F. Gareev0O.A. Beylerli1Zhang Hongli2S. A. Roumiantsev3Central Research Laboratory, Bashkir State Medical University ; Pirogov Russian National Research Medical UniversityCentral Research Laboratory, Bashkir State Medical University ; RUDN UniversityFirst Affiliated Hospital of Harbin Medical University ; Heilongjiang Province Neuroscience InstitutePirogov Russian National Research Medical University ; National Medical Endocrinology Research CentreIntroduction. Glioblastoma exhibits high aggressiveness and complex mechanisms of therapy resistance. Tumor necrosis factor receptor-associated protein 1 (TRAP1) participates in metabolic regulation and tumor cell resistance to apoptosis; however, its role in glioblastoma remains understudied. Materials and methods. Glioma cell lines T98G and human brain astrocytes (HBA) were used as controls. TRAP1 expression was suppressed via the lentiviral transduction method using short hairpin RNA (shRNA). Exosomes were isolated from culture medium by ultracentrifugation and subsequently identified by typical markers (TSG101, CD63, and ALIX). The protein-level expression of TRAP1 and key glycolytic enzymes was analyzed by western blot analysis. Cell viability was assessed using the MTT assay, while apoptosis levels were measured using Annexin V-FITC/PI staining. In addition, ATP production was analyzed using bioluminescent methods. Results and discussion. TRAP1 was overexpressed in T98G cells, including in exosomes, while HBA exhibited moderate to low TRAP1 levels. The suppression of TRAP1 in T98G cells resulted in a decrease in glycolytic enzyme expression, an increase in apoptosis, and a decrease in cell viability. TRAP1 overexpression facilitated metabolic reprogramming toward aerobic glycolysis, along with reducing ATP synthesis. Exosomal TRAP1 likely participates in intercellular communication, promoting tumor adaptation to stress and the formation of a pro-tumor microenvironment. Conclusion. These findings support the pivotal role of TRAP1 in regulating metabolic status and maintaining aggressive phenotypes in glioblastoma. The targeted inhibition of TRAP1 may become a promising therapeutic strategy for glioblastoma, aimed at reducing tumor cell viability and limiting metabolic flexibility.https://www.surgonco.ru/jour/article/view/1084glioblastomatrap1metabolic reprogrammingshrnaexosomesglycolysisapoptosis |
| spellingShingle | I. F. Gareev O.A. Beylerli Zhang Hongli S. A. Roumiantsev Analysis and Functional Significance of TRAP1 in Glioblastoma Креативная хирургия и онкология glioblastoma trap1 metabolic reprogramming shrna exosomes glycolysis apoptosis |
| title | Analysis and Functional Significance of TRAP1 in Glioblastoma |
| title_full | Analysis and Functional Significance of TRAP1 in Glioblastoma |
| title_fullStr | Analysis and Functional Significance of TRAP1 in Glioblastoma |
| title_full_unstemmed | Analysis and Functional Significance of TRAP1 in Glioblastoma |
| title_short | Analysis and Functional Significance of TRAP1 in Glioblastoma |
| title_sort | analysis and functional significance of trap1 in glioblastoma |
| topic | glioblastoma trap1 metabolic reprogramming shrna exosomes glycolysis apoptosis |
| url | https://www.surgonco.ru/jour/article/view/1084 |
| work_keys_str_mv | AT ifgareev analysisandfunctionalsignificanceoftrap1inglioblastoma AT oabeylerli analysisandfunctionalsignificanceoftrap1inglioblastoma AT zhanghongli analysisandfunctionalsignificanceoftrap1inglioblastoma AT saroumiantsev analysisandfunctionalsignificanceoftrap1inglioblastoma |