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PSMB8 regulates glioma cell migration, proliferation, and apoptosis through modulating ERK1/2 and PI3K/AKT signaling
Bing-Ya Yang1, Jing-Wei Song2, Hong-Zhi Sun2
1Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Jiangsu Province Key Laboratory of Modern Pathogen Biology, Nanjing, Jiangsu, 211166, China.
Abstract:
Glioma has been considered as one of the most aggressive and popular brain tumors of patients. It is essential to explore the mechanism of glioma. In this study, we established PSMB8 as a therapeutic target for glioma treatment. Expression of PSMB8 as well as Ki-67 was higher in glioma tissues demonstrated by western blot and immunohistochemistry. Then, the role of PSMB8 in migration and proliferation of glioma cells was investigated by conducting wound-healing, trans-well assay, cell counting kit (CCK)-8, flow cytometry assay and colony formation analysis. The data showed that interfering PSMB8 may inhibit the migration and proliferation of glioma cells by reducing expression of cyclin A, cyclin B1, cyclin D1, Vimentin, and N-cadherin, and by increasing expression of E-cadherin. Additionally, interfering PSMB8 may induce apoptosis of glioma cells by upregulating caspase-3 expression. Furthermore, these in vitro findings were validated in vivo and the ERK1/2 and PI3k/AKT signaling pathways were involved in PSMB8-triggered migration and proliferation of glioma cells. In an in vivo model, downregulation of PSMB8 suppressed tumor growth. In conclusion, PSMB8 is closely associated with migration, proliferation, and apoptosis of glioma cells, and might be considered as a novel prognostic indicator in patients with gliomas.
Insights
Researchers identified PSMB8 as a potential therapeutic target for glioma. Inhibiting PSMB8 suppressed glioma cell migration, proliferation, and tumor growth, suggesting its role in glioma progression.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Research
Background:
- Glioma is an aggressive brain tumor requiring novel therapeutic strategies.
- Understanding glioma pathogenesis is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of PSMB8 in glioma.
- To evaluate PSMB8 as a potential therapeutic target for glioma treatment.
Main Methods:
- Western blot and immunohistochemistry to assess PSMB8 and Ki-67 expression.
- In vitro assays (wound-healing, trans-well, CCK-8, flow cytometry, colony formation) to study cell migration and proliferation.
- In vivo xenograft models to validate findings and assess tumor growth.
- Analysis of signaling pathways (ERK1/2, PI3k/AKT).
Main Results:
- PSMB8 expression was elevated in glioma tissues.
- PSMB8 inhibition reduced glioma cell migration and proliferation by altering key protein expressions (cyclins, cadherins, vimentin).
- PSMB8 downregulation induced glioma cell apoptosis via caspase-3 upregulation.
- In vivo studies confirmed that PSMB8 suppression inhibited tumor growth.
- ERK1/2 and PI3k/AKT pathways were implicated in PSMB8-mediated effects.
Conclusions:
- PSMB8 is significantly associated with glioma cell migration, proliferation, and apoptosis.
- Targeting PSMB8 demonstrates therapeutic potential for glioma.
- PSMB8 may serve as a novel prognostic biomarker for glioma patients.
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