EGFRvIII Promotes the Proneural–Mesenchymal Transition of Glioblastoma Multiforme and Reduces Its Sensitivity to Temozolomide by Regulating the NF-κB/ALDH1A3 Axis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients and Samples
2.2. Cell Culture
2.3. Cell Proliferation and Transwell Migration Assays
2.4. Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR)
2.5. Western Blotting
2.6. Chromatin Immunoprecipitation (ChIP)
2.7. Immunohistochemistry and Immunofluorescence
2.8. In Vivo Xenograft Growth
2.9. Bioluminescence Imaging
2.10. Transcriptome Sequencing
2.11. Statistical Analysis
3. Results
3.1. EGFRvIII Affected the Gene Expression Profile of GBM Patients, and GBM Patients with EGFRvIII (+) Had Low Sensitivity to TMZ
3.2. GBM Cells and Glioma Stem Cells with EGFRvIII (+) Significantly Increased Cell Viability and Cell Migration
3.3. GBM Cells and Glioma Stem Cells with EGFRvIII (+) Significantly Decreased the Expression of PN GBM Markers, Increased the Expression of MES GBM Markers, and Increased the IC50 Value of TMZ
3.4. ALDH1A3 Was Screened and Identified as the Downstream Target Gene of EGFRvIII
3.5. Screening and Determining That the Downstream Signaling Pathway of EGFRvIII Was Related to the NF-κB Pathway, p- NF-κB in EGFRvIII (+) Cells Was Increased, and NF-κB Bound to the ALDH1A3 Promoter Region
3.6. Inhibition of NF-κB Decreased ALDH1A3 Expression of EGFRvIII (+) Cells, Reversed the Enhanced Cell Migration Ability, Decreased the Expression of PN GBM Marker (SOX2), Increased the Expression of MES GBM Marker (CD44), and Increased the IC50 of TMZ Caused by EGFRvIII (+)
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | EGFRvIII (−) n = 15 | EGFRvIII (+) n = 51 | Variation (p-Value) |
---|---|---|---|
Age at diagnosis | 0.2136 a | ||
Mean | 44.13 | 48.92 | |
Standard Deviation | 15.50 | 12.18 | |
Gender | 0.7654 b | ||
Male | 10 | 30 | |
Female | 5 | 21 | |
IDH1 Mutation | 0.9999 b | ||
Mutation | 2 | 9 | |
Wildtype | 13 | 42 | |
Not Available | |||
1p/19q Codeletion Status | 0.9999 b | ||
Codeletion | 0 | 0 | |
Non-Codeletion | 15 | 50 | |
Not Available | 0 | 1 | |
MGMT Promoter Status | 0.2361 b | ||
Methylated | 4 | 24 | |
Un-Methylated | 11 | 27 | |
Not Available | |||
Radiotherapy | 0.4200 b | ||
Yes | 12 | 44 | |
No | 3 | 6 | |
Not Available | 0 | 1 | |
Chemotherapy | 0.2825 b | ||
Yes | 10 | 41 | |
No | 5 | 9 | |
Not Available | 0 | 1 |
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Shi, Z.-F.; Li, G.-Z.; Zhai, Y.; Pan, C.-Q.; Wang, D.; Yu, M.-C.; Liu, C.; Zhang, W.; Yu, X.-G. EGFRvIII Promotes the Proneural–Mesenchymal Transition of Glioblastoma Multiforme and Reduces Its Sensitivity to Temozolomide by Regulating the NF-κB/ALDH1A3 Axis. Genes 2023, 14, 651. https://doi.org/10.3390/genes14030651
Shi Z-F, Li G-Z, Zhai Y, Pan C-Q, Wang D, Yu M-C, Liu C, Zhang W, Yu X-G. EGFRvIII Promotes the Proneural–Mesenchymal Transition of Glioblastoma Multiforme and Reduces Its Sensitivity to Temozolomide by Regulating the NF-κB/ALDH1A3 Axis. Genes. 2023; 14(3):651. https://doi.org/10.3390/genes14030651
Chicago/Turabian StyleShi, Zhong-Fang, Guan-Zhang Li, You Zhai, Chang-Qing Pan, Di Wang, Ming-Chen Yu, Chi Liu, Wei Zhang, and Xiao-Guang Yu. 2023. "EGFRvIII Promotes the Proneural–Mesenchymal Transition of Glioblastoma Multiforme and Reduces Its Sensitivity to Temozolomide by Regulating the NF-κB/ALDH1A3 Axis" Genes 14, no. 3: 651. https://doi.org/10.3390/genes14030651
APA StyleShi, Z.-F., Li, G.-Z., Zhai, Y., Pan, C.-Q., Wang, D., Yu, M.-C., Liu, C., Zhang, W., & Yu, X.-G. (2023). EGFRvIII Promotes the Proneural–Mesenchymal Transition of Glioblastoma Multiforme and Reduces Its Sensitivity to Temozolomide by Regulating the NF-κB/ALDH1A3 Axis. Genes, 14(3), 651. https://doi.org/10.3390/genes14030651