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RNF7-Mediated ROS Targets Malignant Phenotype and Radiotherapy Sensitivity in Glioma With Different IDH1 Genotypes
Yiran Tao1,2, Zimin Shi1,2, Xianyin Liang1,2
1Department of Neurosurgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, The People's Republic of China.
Abstract:
RNF7 (Ring Finger Protein 7) is a key component of CRLs (Cullin-RING-type E3 ubiquitin ligases) and has been found to possess intrinsic anti-ROS capabilities. Aberrant expression of RNF7 has been observed in various tumor types and is known to significantly influence tumor initiation and progression. However, the specific role of RNF7 in glioblastoma remains unclear. IDH (isocitrate dehydrogenase) mutations, which induce metabolic reprogramming and result in notable heterogeneity among glioma with different IDH genotypes. Through analysis of public glioma databases, we identified a high expression of RNF7 in glioma and its correlation with patient prognosis. Moreover, we observed variations in RNF7 expression and its association with patient outcomes under different treatment modalities among different IDH genotypes. In this study, we demonstrated the critical role of RNF7 in the malignant phenotype of IDH1-mutant glioma and its contribution to radiation resistance. Subsequent functional enrichment analysis of RNF7 in glioma, coupled with validation through cellular experiments, confirmed its significant involvement in maintaining redox balance. Our findings suggest that RNF7 exerts a buffering effect against radiation-induced oxidative stress and counterbalances the redox stress induced by IDH1 mutation through its anti-ROS activity. Additionally, our follow-up investigations revealed that the upregulation of RNF7 after radiation exposure and in IDH1-mutant glioma cells is induced by ROS. Collectively, our study underscores the potential of RNF7 as a molecular biomarker in glioma. Elevated RNF7 expression often indicates a heightened metabolic resilience in glioma, leading to resistance against radiotherapy.
Insights
Ring Finger Protein 7 (RNF7) is highly expressed in glioma, promoting malignant phenotypes and radiation resistance in IDH1-mutant tumors by buffering oxidative stress. RNF7 may serve as a key biomarker for glioma treatment response.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Ring Finger Protein 7 (RNF7) is integral to Cullin-RING-type E3 ubiquitin ligases (CRLs) and possesses intrinsic antioxidant properties.
- Aberrant RNF7 expression is implicated in tumorigenesis, but its specific role in glioblastoma, particularly concerning isocitrate dehydrogenase (IDH) mutations, is not well-defined.
- IDH mutations drive metabolic reprogramming in glioma, contributing to significant genotypic heterogeneity.
Purpose of the Study:
- To investigate the role and prognostic significance of RNF7 in glioblastoma.
- To elucidate the functional involvement of RNF7 in the malignant phenotype and treatment resistance of IDH1-mutant glioma.
- To explore the relationship between RNF7, redox balance, and response to radiation therapy.
Main Methods:
- Analysis of public glioma databases to assess RNF7 expression and its correlation with patient prognosis and treatment outcomes across different IDH genotypes.
- Functional enrichment analysis of RNF7 in glioma.
- In vitro cellular experiments to validate RNF7's role in redox balance and response to oxidative stress and radiation.
Main Results:
- RNF7 is highly expressed in glioma, correlating with poorer patient prognosis.
- RNF7 expression and its prognostic association vary among different IDH genotypes and treatment modalities.
- RNF7 plays a critical role in the malignant phenotype of IDH1-mutant glioma, contributing to radiation resistance by maintaining redox balance and buffering ROS-induced oxidative stress.
- RNF7 upregulation post-radiation and in IDH1-mutant glioma is induced by ROS.
Conclusions:
- RNF7 is a key driver of malignant phenotypes and radiation resistance in IDH1-mutant glioma.
- RNF7's anti-ROS activity is crucial for maintaining redox homeostasis and conferring metabolic resilience against oxidative stress.
- RNF7 serves as a potential molecular biomarker for predicting glioma radiosensitivity and treatment outcomes.
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