High SOX9 Maintains Glioma Stem Cell Activity through a Regulatory Loop Involving STAT3 and PML
Abstract
:1. Introduction
2. Results
2.1. High SOX9 Levels Correlate with Lower Patient Survival
2.2. SOX9 Upregulation Increases Tumorigenic Capacity of GSCs
2.3. SOX9 Downregulation Decreases Stemness and Tumorigenic Capacity in GSCs
2.4. Transcriptomic Analysis Reveals STAT3 and PML as Mediators of SOX9 Activity in GSCs
2.5. STAT3 Regulates GSC Activity and Its Pharmacological Inhibition Reduces Tumorigenicity
2.6. PML Regulates GSC Activity and Its Pharmacological Inhibition Reduces Tumorigenicity
2.7. The SOX9–STAT3–PML Axis Constitutes a Regulatory Loop That Modulates GSCs
3. Discussion
4. Materials and Methods
4.1. Human Subjects
4.2. Tissue Microarrays
4.3. Cell Culture
4.4. Gene Silencing and Overexpression
4.5. Cell Proliferation Assay
4.6. Oncosphere Formation Assay
4.7. Senescence-Associated β-Galactosidase Staining
4.8. Cell Viability Assay
4.9. Quantitative Real-Time PCR
4.10. Immunoblot
4.11. Immunofluorescence
4.12. In Vivo Carcinogenesis Assays
4.13. Immunohistochemistry
4.14. Transcriptome Analysis
4.15. Chromatin Immunoprecipitation Assay
4.16. Data Availability Statement
4.17. Data Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Aldaz, P.; Martín-Martín, N.; Saenz-Antoñanzas, A.; Carrasco-Garcia, E.; Álvarez-Satta, M.; Elúa-Pinin, A.; Pollard, S.M.; Lawrie, C.H.; Moreno-Valladares, M.; Samprón, N.; et al. High SOX9 Maintains Glioma Stem Cell Activity through a Regulatory Loop Involving STAT3 and PML. Int. J. Mol. Sci. 2022, 23, 4511. https://doi.org/10.3390/ijms23094511
Aldaz P, Martín-Martín N, Saenz-Antoñanzas A, Carrasco-Garcia E, Álvarez-Satta M, Elúa-Pinin A, Pollard SM, Lawrie CH, Moreno-Valladares M, Samprón N, et al. High SOX9 Maintains Glioma Stem Cell Activity through a Regulatory Loop Involving STAT3 and PML. International Journal of Molecular Sciences. 2022; 23(9):4511. https://doi.org/10.3390/ijms23094511
Chicago/Turabian StyleAldaz, Paula, Natalia Martín-Martín, Ander Saenz-Antoñanzas, Estefania Carrasco-Garcia, María Álvarez-Satta, Alejandro Elúa-Pinin, Steven M. Pollard, Charles H. Lawrie, Manuel Moreno-Valladares, Nicolás Samprón, and et al. 2022. "High SOX9 Maintains Glioma Stem Cell Activity through a Regulatory Loop Involving STAT3 and PML" International Journal of Molecular Sciences 23, no. 9: 4511. https://doi.org/10.3390/ijms23094511