{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T09:13:48Z","timestamp":1789204428186,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T00:00:00Z","timestamp":1760227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UPWR 2.0:international and interdisciplinary program of development of Wroc\u0142aw University of Environmental and Life Sciences","award":["POWR.03.05.00-00-Z062\/18"],"award-info":[{"award-number":["POWR.03.05.00-00-Z062\/18"]}]},{"DOI":"10.13039\/100016247","name":"Wroc\u0142aw University of Environmental and Life Sciences","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100016247","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>G-quadruplexes have been identified as a promising anti-cancer target because of their ability to modulate the stability of mRNAs encoding oncogenes, tumor suppressor genes, and other potential therapeutic targets. Deregulation of DNA damage and Unfolded Protein Response pathways in cancer cells may create vulnerabilities that can be exploited therapeutically. Previous studies have shown variations in the relative expression of DDR and UPR components in canine lymphoma and leukemia cell lines CLBL-1, CLB70, and GL-1. In the present study, we report the presence of G-quadruplex structures in these canine cell lines. Downregulation of the expression of DDR and UPR components at the mRNA level was observed in the CLBL-1 and CLB70 cell lines after stabilization of G4 structures using the ligand PhenDC3. In contrast, in GL-1 cells, important components of the DDR pathway, such as PARP1, GADD45A, and PIK3CB were upregulated in response to PhenDC3 treatment. Downregulation of DDIT4 mRNA expression, which encodes an important UPR component, was detected in the CLBL-1 and GL-1 cell lines after PhenDC3 exposure. These results suggest that G4 structures can be used to manipulate the expression of potential targets to treat lymphoma in dogs. A substantial enrichment of DNA replication and pyrimidine metabolism pathways was found in the GL-1 cell line after G4 stabilization. This finding suggests that PhenDC3 may induce DNA replication stress in this cell line. Collectively, these results support the feasibility of employing canine cancer cells as a model system to investigate the role of G-quadruplex structures in cancer.<\/jats:p>","DOI":"10.3390\/ijms26209928","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T16:13:03Z","timestamp":1760717583000},"page":"9928","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Stabilization of G-Quadruplexes Modulates the Expression of DNA Damage and Unfolded Protein Response Genes in Canine Lymphoma\/Leukemia Cells"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5377-6609","authenticated-orcid":false,"given":"Beatriz","family":"Hern\u00e1ndez-Su\u00e1rez","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland"},{"name":"IRSD\u2014Institut de Recherche en Sant\u00e9 Digestive, Universit\u00e9 de Toulouse, INSERM, INRAE, ENVT, UPS, 31300 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Gillespie","sequence":"additional","affiliation":[{"name":"Instituto de Tecnolog\u00edas Biom\u00e9dicas, Facultad de Medicina, Campus Ciencias de la Salud, Universidad de La Laguna, 38071 La Laguna, Tenerife, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9509-4845","authenticated-orcid":false,"given":"Ewa","family":"Dejnaka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9511-3504","authenticated-orcid":false,"given":"Bo\u017cena","family":"Obmi\u0144ska-Mrukowicz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7449-1661","authenticated-orcid":false,"given":"Aleksandra","family":"Pawlak","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland"},{"name":"Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602, USA"},{"name":"SMART Pharmacology, Precision One Health Initiative, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.tibs.2020.11.001","article-title":"G-Quadruplexes in RNA Biology: Recent Advances and Future Directions","volume":"46","author":"Dumas","year":"2021","journal-title":"Trends Biochem. 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