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Published on: March 28, 2021
Receptor-Interacting Protein 140 Enhanced Temozolomide-Induced Cellular Apoptosis Through Regulation of E2F1 in Human
Hong-Chieh Tsai1,2, Kuo-Chen Wei3,4, Pin-Yuan Chen4,5
1Department of Neurosurgery, Linkou Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan.
Abstract:
Glioblastoma (GBM), a grade IV glioma, is responsible for the highest years of potential life lost among cancers. The poor prognosis is attributable to its high recurrence rate, caused in part by the development of resistance to chemotherapy. Receptor-interacting protein 140 (RIP140) is a very versatile coregulator of nuclear receptors and transcription factors. Although many of the pathways regulated by RIP140 contribute significantly to cancer progression, the function of RIP140 in GBM remains to be determined. In this study, we found that higher RIP140 expression was associated with prolonged survival in patients with newly diagnosed GBM. Intracellular RIP140 levels were increased after E2F1 activation following temozolomide (TMZ) treatment, which in turn modulated the expression of E2F1-targeted apoptosis-related genes. Overexpression of RIP140 reduced glioma cell proliferation and migration, induced cellular apoptosis, and sensitized GBM cells to TMZ. Conversely, knockdown of RIP140 increased TMZ resistance. Taken together, our results suggest that RIP140 prolongs the survival of patients with GBM both by inhibiting tumor cell proliferation and migration and by increasing cellular sensitivity to chemotherapy. This study helps improve our understanding of glioma recurrence and may facilitate the development of more effective treatments.
Insights
Receptor-interacting protein 140 (RIP140) enhances glioblastoma (GBM) patient survival by inhibiting tumor growth and increasing chemotherapy sensitivity. Higher RIP140 levels correlate with better outcomes in newly diagnosed GBM.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Glioblastoma (GBM) is an aggressive brain cancer with high recurrence and poor prognosis.
- Chemotherapy resistance significantly contributes to GBM recurrence.
- Receptor-interacting protein 140 (RIP140) is a nuclear receptor co-regulator with known roles in cancer, but its function in GBM is unclear.
Purpose of the Study:
- To investigate the role of Receptor-interacting protein 140 (RIP140) in glioblastoma (GBM).
- To determine the association between RIP140 expression and patient survival in GBM.
- To elucidate the mechanisms by which RIP140 affects GBM cell behavior and response to chemotherapy.
Main Methods:
- Analysis of RIP140 expression in relation to patient survival data.
- Investigation of RIP140 expression changes following temozolomide (TMZ) treatment.
- Assessment of RIP140's effects on glioma cell proliferation, migration, and apoptosis.
- Evaluation of RIP140's impact on GBM cell sensitivity to TMZ.
Main Results:
- Higher RIP140 expression was associated with prolonged survival in newly diagnosed GBM patients.
- Temozolomide (TMZ) treatment increased intracellular RIP140 levels, modulating apoptosis-related gene expression.
- RIP140 overexpression inhibited glioma cell proliferation and migration, induced apoptosis, and sensitized cells to TMZ.
- Knockdown of RIP140 led to increased TMZ resistance in GBM cells.
Conclusions:
- RIP140 plays a protective role in glioblastoma, prolonging patient survival.
- RIP140 inhibits tumor progression and enhances sensitivity to chemotherapy, specifically temozolomide.
- Targeting RIP140 may offer a therapeutic strategy to overcome GBM recurrence and improve treatment efficacy.
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