Validation of protein arginine methyltransferase 5 (PRMT5) as a candidate therapeutic target in the spontaneous canine model of non-Hodgkin lymphoma

Autor: Kris Vaddi, Xiaoli Zhang, Lapo Alinari, Hatice Gulcin Ozer, Fiona Brown, Mackenzie E. Long, Kyle A. Renaldo, Ayse Selen Yilmaz, Peggy Scherle, Brett Klamer, Sarah Schlotter, Victor E. Valli, Konstantin Shilo, Lindsay E. Courtney, Shelby Sloan, William C. Kisseberth, Youssef Youssef, Robert A. Baiocchi, Jihyun Chung
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Protein-Arginine N-Methyltransferases
B Cells
Arginine
Lymphoma
Microarrays
Cancer Treatment
Gene Expression
Apoptosis
medicine.disease_cause
Malignant transformation
Hematologic Cancers and Related Disorders
White Blood Cells
0302 clinical medicine
Animal Cells
immune system diseases
hemic and lymphatic diseases
Medicine and Health Sciences
Cultured Tumor Cells
Staining
Canine Lymphoma
Multidisciplinary
Tissue microarray
Chromosome Biology
T Cells
Protein arginine methyltransferase 5
Lymphoma
Non-Hodgkin
Hematology
Chromatin
Bioassays and Physiological Analysis
Oncology
030220 oncology & carcinogenesis
Medicine
Epigenetics
Biological Cultures
Cellular Types
Research Article
Immune Cells
Science
Immunology
Antineoplastic Agents
Biology
Research and Analysis Methods
Methylation
03 medical and health sciences
Dogs
Cell Line
Tumor
medicine
Genetics
Animals
Humans
Antibody-Producing Cells
Cell Proliferation
Blood Cells
Lymphoma Cells
Cancers and Neoplasms
Biology and Life Sciences
Cell Biology
Cell Cultures
medicine.disease
Nuclear Staining
Disease Models
Animal
030104 developmental biology
Specimen Preparation and Treatment
Cancer research
Carcinogenesis
Zdroj: PLoS ONE, Vol 16, Iss 5, p e0250839 (2021)
PLoS ONE
ISSN: 1932-6203
Popis: Non-Hodgkin lymphoma (NHL) is a heterogeneous group of blood cancers arising in lymphoid tissues that commonly effects both humans and dogs. Protein arginine methyltransferase 5 (PRMT5), an enzyme that catalyzes the symmetric di-methylation of arginine residues, is frequently overexpressed and dysregulated in both human solid and hematologic malignancies. In human lymphoma, PRMT5 is a known driver of malignant transformation and oncogenesis, however, the expression and role of PRMT5 in canine lymphoma has not been explored. To explore canine lymphoma as a useful comparison to human lymphoma while validating PRMT5 as a rational therapeutic target in both, we characterized expression patterns of PRMT5 in canine lymphoma tissue microarrays, primary lymphoid biopsies, and canine lymphoma-derived cell lines. The inhibition of PRMT5 led to growth suppression and induction of apoptosis, while selectively decreasing global marks of symmetric dimethylarginine (SDMA) and histone H4 arginine 3 symmetric dimethylation. We performed ATAC-sequencing and gene expression microarrays with pathway enrichment analysis to characterize genome-wide changes in chromatin accessibility and whole-transcriptome changes in canine lymphoma cells lines upon PRMT5 inhibition. This work validates PRMT5 as a promising therapeutic target for canine lymphoma and supports the continued use of the spontaneously occurring canine lymphoma model for the preclinical development of PRMT5 inhibitors for the treatment of human NHL.
Databáze: OpenAIRE
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