IARC 60th Anniversary - 19-21 May 2026
Session : 19/05/26 - Posters
Stabilization of G-Quadruplexes Modulates the Expression of DNA Damage and Unfolded Protein Response Genes in Canine Lymphoma/Leukemia Cells
HERNANDEZ SUAREZ B. 1,2, GILLESPIE D. 3, DEJNAKA E. 2, OBMINSKA-MRUKOWICZ B. 2, PAWLAK A. 2,4,5
1 IRSD (DIGESTIVE HEALTH RESEARCH INSTITUTE), Toulouse, France; 2 Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland; 3 Instituto de Tecnologías Biomédicas, Facultad de Medicina, Campus Ciencias de la Salud, Universidad de La Laguna, La Laguna, Spain; 4 Department of Physiology and Pharmacology, University of Georgia, Athens, United States; 5 SMART Pharmacology, Precision One Health Initiative, University of Georgia, Athens, United States
Background: G-quadruplexes are non-canonical structures formed by tetrads of guanines that are key regulators of cellular processes (1). In the last years, G4 structures have been researched as possible therapeutic target due to their role in modulating the translation of oncogenes’ mRNAs (2). G4 structures can also interfere with DNA replication and repair, leading to increased DNA damage and replication stress (3). DNA damage and Unfolded protein reponses are key pathways of the cell which are usually altered in cancer. In this research, it is studied the connection between DDR and UPR alterations by G4 stabilization in canine cancer cells.
Objectives: Study the stabilization of G4 structures in canine lymphoma and leukemia cell lines CLBL-1, CLB70, and GL-1 and their roles in regulating DDR and UPR pathways.
Methods: Cells were treated with DMSO or PhenDC3 at 5 µM concentration for 24 h. A portion of the cells were collected in TRIzol reagent to extract RNA for further qPCR analysis or to be sequenced by Novogene (UK).
Results: An observed downregulation of the expression of DDR and UPR components at the mRNA level in the CLBL-1 and CLB70 cell lines after stabilization of G4 structures using the ligand PhenDC3. In contrast, in GL-1 cells, some targets of the DDR pathway, such as PARP1, GADD45A, and PIK3CB were upregulated in response to PhenDC3 treatment. Downregulation of mRNA expression of an important UPR component - DDIT4 - was detected in the CLBL-1 and GL-1 cell lines when treated with PhenDC3. A substantial enrichment of DNA replication and pyrimidine metabolism pathways was found in the GL-1 cell line after G4 stabilization.
Conclusions: These results suggest that G4 structures can be used to manipulate the expression of potential targets to treat lymphoma in dogs. PhenDC3 may induce DNA replication stress in GL-1 line. Collectively, these results support the feasibility of using canine cancer cells as a model system to investigate the role of G-quadruplex (G4) structures in cancer.
Published research (4)
(1) Cammas A, Millevoi S. RNA G-quadruplexes: emerging mechanisms in disease. Nucleic Acids Res. 2017 Feb 28;45(4):1584-1595. doi: 10.1093/nar/gkw1280. PMID: 28013268; PMCID: PMC5389700.
(2) Cammas A, Desprairies A, Dassi E, Millevoi S. The shaping of mRNA translation plasticity by RNA G-quadruplexes in cancer progression and therapy resistance. NAR Cancer. 2024 May 31;6(2):zcae025. doi: 10.1093/narcan/zcae025. PMID: 38828391; PMCID: PMC11140630.
(3) Linke, R.; Limmer, M.; Juranek, S.; Heine, A.; Paeschke, K. The Relevance of G-Quadruplexes for DNA Repair. Int. J. Mol. Sci. 2021, 22, 12599. https://doi.org/10.3390/ijms222212599.
(4) Hernández-Suárez B, Gillespie DA, Dejnaka E, Obmi?ska-Mrukowicz B, Pawlak A. Stabilization of G-Quadruplexes Modulates the Expression of DNA Damage and Unfolded Protein Response Genes in Canine Lymphoma/Leukemia Cells. Int J Mol Sci. 2025 Oct 12;26(20):9928. doi: 10.3390/ijms26209928. PMID: 41155228; PMCID: PMC12563012.