Short-Term TERT Inhibition Impairs Cellular Proliferation via a Telomere Length-Independent Mechanism and Can Be Exploited as a Potential Anticancer Approach
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Compounds
2.2. Cell Cultures
2.3. Animals
2.4. Plasmids and Transfection
2.5. Reverse Transcription and Quantitative Real-Time PCR
2.6. Immunoblot and Co-Immunoprecipitation
2.7. Nuclear and Cytoplasmic Fraction
2.8. Immunofluorescence
2.9. Cell Viability and Cell Cycle Analysis
2.10. Telomere Length Measurement
2.11. Xenotransplantation of LCL and BL Cells in Zebrafish Embryos
2.12. Embryo Dissociation and Flow Cytometric Analysis
2.13. Statistical Analyses
3. Results
3.1. TERT Inhibition Reduced Nuclear Levels of p65
3.2. TERT Inhibition by BIBR Suppressed Transcription of a Subset of NF-κB Target Genes, including MYC
3.3. MYC Deregulation Mediated by TERT Inhibition Was Independent of WNT/β-Catenin Signalling, and TERT and MYC Did Not Interact at the Protein Level
3.4. Ectopic TERT Expression Activated Transcription of NF-κB Target Genes
3.5. p65 Inhibition Recapitulated the Effects of TERT Inhibition
3.6. TERT Inhibition Promoted P21 Expression and Nuclear Localization
3.7. Short-Term Tert Inhibition by BIBR in Zebrafish Reduced Myc and Increased p21 Expression
3.8. Anti-Proliferative Effects of Combined Treatment with BIBR and FLU or CY in EBV-Immortalized and Fully Transformed B Cells Xenografted in Zebrafish
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Amin, A.; Morello, M.; Petrara, M.R.; Rizzo, B.; Argenton, F.; De Rossi, A.; Giunco, S. Short-Term TERT Inhibition Impairs Cellular Proliferation via a Telomere Length-Independent Mechanism and Can Be Exploited as a Potential Anticancer Approach. Cancers 2023, 15, 2673. https://doi.org/10.3390/cancers15102673
Amin A, Morello M, Petrara MR, Rizzo B, Argenton F, De Rossi A, Giunco S. Short-Term TERT Inhibition Impairs Cellular Proliferation via a Telomere Length-Independent Mechanism and Can Be Exploited as a Potential Anticancer Approach. Cancers. 2023; 15(10):2673. https://doi.org/10.3390/cancers15102673
Chicago/Turabian StyleAmin, Aamir, Marzia Morello, Maria Raffaella Petrara, Beatrice Rizzo, Francesco Argenton, Anita De Rossi, and Silvia Giunco. 2023. "Short-Term TERT Inhibition Impairs Cellular Proliferation via a Telomere Length-Independent Mechanism and Can Be Exploited as a Potential Anticancer Approach" Cancers 15, no. 10: 2673. https://doi.org/10.3390/cancers15102673