Transcriptome profiling of Canine Parvovirus 2 Nonstructural gene 1(CPV2.NS1) transfected 4T1 mice mammary tumor cells to elucidate its oncolytic effects.

Autor: Arora R; Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar, India; Department of Veterinary Biochemistry, College of Veterinary and Animal Sciences, Kishanganj, BASU, Patna, India., Malla WA; Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar, India., Tyagi A; GB Pant University of Agriculture and Technology, Pantnagar, India., Saxena S; Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar, India., Mahajan S; Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar, India., Sajjanar B; Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar, India., Gandham R; Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar, India., Tiwari AK; ICAR - Central Avian Research Institute, Izatnagar, India.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Nov; Vol. 281 (Pt 4), pp. 136620. Date of Electronic Publication: 2024 Oct 16.
DOI: 10.1016/j.ijbiomac.2024.136620
Abstrakt: Oncolytic viral gene therapy is a directed approach to target cancer cells without affecting healthy cells of the body. Canine parvovirus (CPV2) is an oncolytic virus that precisely targets and destroys neoplastic cells by causing DNA damage, mitochondrial damage, and apoptosis. Non-structural gene 1 (NS1) of CPV, concerned with viral DNA replication is a key mediator of cytotoxicity of CPV and can specifically cause tumor cell lysis. In the present study, by using the transcriptomics approach, we tried to identify molecular pathways and key genes involved in CPV2.NS1 mediated 4T1 mice mammary tumor cell death. We identified necroptosis and mitochondrial damage-mediated apoptosis as major cell death pathways leading to CPV2.NS1 transfected 4T1 cancer cell death. Various DEGs identified in our study play an important role in pathways like the PI3K/AKT pathway, diverse metabolic pathways, MAPK signaling pathway, and FGF signaling pathway, whichare mostly dysregulated in cancerous conditions. Histone variant H2A.X genes, Capn2, and Mapk10/JNK are predicted as key genes that play a role in causing endoplasmic reticulum stress and mitochondrial damage, thereby leading to necroptosis and apoptosis. This study is a preliminary work done to identify key genes and molecular pathways involved in CPV2.NS1 mediated 4T1 cancer cells death which need to be further validated to establish this viral gene as a potent oncolytic agent.
Competing Interests: Declaration of competing interest All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work report of the article submitted.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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