Drug Resistance in Medulloblastoma Is Driven by YB-1, ABCB1 and a Seven-Gene Drug Signature
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Lines and Standard Culture Conditions
2.2. Cytotoxicity Assays
2.3. Establishment of Drug-Tolerant Cell Lines
2.4. Quantitative Real-Time PCR Analysis
2.5. Western Blotting
2.6. Modified Transwell Invasion Assay
2.7. shRNA Transduction
2.8. Chromatin Immunoprecipitation
2.9. Whole Transcriptome Sequencing
2.10. 3′mRNA Sequencing
2.11. Statistical Analysis
2.12. Bioinformatic Analysis of Published Datasets
3. Results
3.1. High YB-1 Expression Correlates with Poor Overall Survival in Medulloblastoma
3.2. YB-1 Depletion Impedes the Invasive Capability of Medulloblastoma Cells
3.3. YB-1 Functions in Numerous Key Cellular Pathways in Medulloblastoma Cells
3.4. YB-1 Inhibition Is Associated with Increased Cellular Sensitivity to Vincristine, Partly through Reduced Expression of ABCB1
3.5. Drug-Tolerant Medulloblastoma Cell Lines Exhibit a Common Gene Signature Associated with Chemoresistance
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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Taylor, L.; Wade, P.K.; Johnson, J.E.C.; Aldighieri, M.; Morlando, S.; Di Leva, G.; Kerr, I.D.; Coyle, B. Drug Resistance in Medulloblastoma Is Driven by YB-1, ABCB1 and a Seven-Gene Drug Signature. Cancers 2023, 15, 1086. https://doi.org/10.3390/cancers15041086
Taylor L, Wade PK, Johnson JEC, Aldighieri M, Morlando S, Di Leva G, Kerr ID, Coyle B. Drug Resistance in Medulloblastoma Is Driven by YB-1, ABCB1 and a Seven-Gene Drug Signature. Cancers. 2023; 15(4):1086. https://doi.org/10.3390/cancers15041086
Chicago/Turabian StyleTaylor, Louisa, Philippa K. Wade, James E. C. Johnson, Macha Aldighieri, Sonia Morlando, Gianpiero Di Leva, Ian D. Kerr, and Beth Coyle. 2023. "Drug Resistance in Medulloblastoma Is Driven by YB-1, ABCB1 and a Seven-Gene Drug Signature" Cancers 15, no. 4: 1086. https://doi.org/10.3390/cancers15041086