Evidence map›Paper›PMID 33989303›Full record

ArticlePloS one2021

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

Shelby L Sloan, Kyle A Renaldo, Mackenzie Long, Ji-Hyun Chung, Lindsay E Courtney, Konstantin Shilo, Youssef Youssef, Sarah Schlotter, Fiona Brown, Brett G Klamer and 9 more

Open access · goldAbstract readValidation Study
In one paragraph

Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.5field-weighted citation impact, top 39% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 2 institutions in 1 country.

Shelby L SloanDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States of America.ORCID 0000-0001-7366-9184
Kyle A RenaldoDepartment of Veterinary Clinical Sciences, The Ohio State University, Columbus, Ohio, United States of America.
Mackenzie LongDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States of America.
Ji-Hyun ChungDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America.
Lindsay E CourtneyDepartment of Veterinary Clinical Sciences, The Ohio State University, Columbus, Ohio, United States of America.
Konstantin ShiloDepartment of Pathology, The Ohio State University, Columbus, Ohio, United States of America.ORCID 0000-0002-6702-3130
Youssef YoussefDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America.
Sarah SchlotterDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America.
Fiona BrownDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America.
Brett G KlamerDepartment of Biomedical Informatics, Center for Biostatistics, The Ohio State University, Columbus, Ohio, United States of America.
Xiaoli ZhangDepartment of Biomedical Informatics, Center for Biostatistics, The Ohio State University, Columbus, Ohio, United States of America.
Ayse S YilmazDepartment of Biomedical Informatics, Center for Biostatistics, The Ohio State University, Columbus, Ohio, United States of America.
Hatice G OzerDepartment of Biomedical Informatics, Center for Biostatistics, The Ohio State University, Columbus, Ohio, United States of America.
Victor E ValliVDx Veterinary Diagnostics, Davis, California, United States of America.
Kris VaddiPrelude Therapeutics, Wilmington, Delaware, United States of America.
Peggy ScherlePrelude Therapeutics, Wilmington, Delaware, United States of America.
Lapo AlinariDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America.
William C KisseberthDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America.
Robert A BaiocchiDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America.
The Ohio State University · USIVDiagnostics (United States) · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Jennifer A. Woyach · 1985 to 2026
$132.3M
The OSU Center for Clinical and Translational Science: Advancing Today's Discoveries to Improve HealthUL1TR002733 · NCATS · OHIO STATE UNIVERSITY · PI RINGEL, MATTHEW D · 2018 to 2022
$28.9M
NCATS NIH HHS UL1 TR002733NCI NIH HHS P30 CA016058
6 · The paper itself

Abstract

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.

Indexed as

AnimalsAntineoplastic AgentsApoptosisCell Line, TumorCell ProliferationDisease Models, AnimalDogsHumansLymphoma, Non-HodgkinMethylationProtein-Arginine N-MethyltransferasesAntineoplastic AgentsPRMT5 protein, humanProtein-Arginine N-Methyltransferases

Identifiers

PMID33989303
PMCPMC8121334
OpenAlexW3160465333

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.