Hypermethylation-Mediated Silencing of CIDEA, MAL and PCDH17 Tumour Suppressor Genes in Canine DLBCL: From Multi-Omics Analyses to Mechanistic Studies
Abstract
:1. Introduction
2. Results
2.1. Identification of Putative TSGs Deregulated in cDLBCL
2.2. CiDEA, MAL and PCDH17 mRNA Expression Is Restored by HDs and HDACis in Both CLBL-1 Cells and cDLBCL Primary Cell Cultures
2.3. CiDEA, MAL and PCDH17 Are Confirmed to Be Aberrantly Hypermethylated in CLBL-1 and PCC Cells
2.4. CiDEA and MAL Protein Expression Is Restored by AZA + VAL in CLBL-1 Cells
2.5. In Vitro Methylation of CiDEA, MAL and PCDH17 CpG Sites Affects Gene Transcription
2.6. Transcription Factor Binding Sites Putatively Iinvolved in CiDEA, MAL and PCDH17 Methylation-Dependent Silencing
3. Discussion
4. Materials and Methods
4.1. Chemicals and Reagents
4.2. Candidate Genes Selection
4.3. Canine B-Cell Lymphoma Cell Lines
4.4. Cell Treatments
4.5. Cytotoxicity
4.6. Quantitative Real-Time PCR (qPCR)
4.7. Methyl Specific PCR (MSP)
4.8. Total Protein Isolation and Immunoblotting
4.9. Cloning of CiDEA, MAL and PCDH17 CpG-Rich Genomic Regions
4.10. Promoter Reporter Assays
4.11. In Vitro Methylation
4.12. In Silico Predictive Analysis
4.13. Statistical 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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Zorzan, E.; Elgendy, R.; Guerra, G.; Da Ros, S.; Gelain, M.E.; Bonsembiante, F.; Garaffo, G.; Vitale, N.; Piva, R.; Marconato, L.; et al. Hypermethylation-Mediated Silencing of CIDEA, MAL and PCDH17 Tumour Suppressor Genes in Canine DLBCL: From Multi-Omics Analyses to Mechanistic Studies. Int. J. Mol. Sci. 2022, 23, 4021. https://doi.org/10.3390/ijms23074021
Zorzan E, Elgendy R, Guerra G, Da Ros S, Gelain ME, Bonsembiante F, Garaffo G, Vitale N, Piva R, Marconato L, et al. Hypermethylation-Mediated Silencing of CIDEA, MAL and PCDH17 Tumour Suppressor Genes in Canine DLBCL: From Multi-Omics Analyses to Mechanistic Studies. International Journal of Molecular Sciences. 2022; 23(7):4021. https://doi.org/10.3390/ijms23074021
Chicago/Turabian StyleZorzan, Eleonora, Ramy Elgendy, Giorgia Guerra, Silvia Da Ros, Maria Elena Gelain, Federico Bonsembiante, Giulia Garaffo, Nicoletta Vitale, Roberto Piva, Laura Marconato, and et al. 2022. "Hypermethylation-Mediated Silencing of CIDEA, MAL and PCDH17 Tumour Suppressor Genes in Canine DLBCL: From Multi-Omics Analyses to Mechanistic Studies" International Journal of Molecular Sciences 23, no. 7: 4021. https://doi.org/10.3390/ijms23074021