Evidence map›Paper›PMID 31694585›Full record

ArticleBMC cancer2019

Role of protein arginine methyltransferase 5 in group 3 (MYC-driven) Medulloblastoma.

Nagendra K Chaturvedi, Sidharth Mahapatra, Varun Kesherwani, Matthew J Kling, Mamta Shukla, Sutapa Ray, Ranjana Kanchan, Naveenkumar Perumal, Timothy R McGuire, J Graham Sharp and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

23 citing papers in PubMed, 32 citations in OpenAlex.

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  19. Protein Arginine Methyltransferase 5 FunctionsFrontiers in cell and developmental biology · 2021
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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

12 authors at 2 institutions in 1 country.

Nagendra K ChaturvediDepartment of Pediatrics, Division of Hematology and Oncology, University of Nebraska Medical Center, Omaha, NE, 68198, USA. nchaturvedi@unmc.edu.ORCID http://orcid.org/0000-0001-7037-898X
Sidharth MahapatraDepartment of Pediatrics, Division of Hematology and Oncology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Varun KesherwaniChild Health Research Institute Cancer, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Matthew J KlingDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Mamta ShuklaDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Sutapa RayDepartment of Pediatrics, Division of Hematology and Oncology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Ranjana KanchanDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Naveenkumar PerumalDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Timothy R McGuireDepartment of Pharmacy Practice, University of Nebraska Medical Center, Omaha, NE, 69198, USA.
J Graham SharpDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Shantaram S JoshiDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Don W CoulterDepartment of Pediatrics, Division of Hematology and Oncology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
University of Nebraska Medical Center · USNebraska Medical Center · US

Funding

UNMC/EPPLEY CANCER CENTER SUPPORT GRANTP30CA036727 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Joann B. Sweasy · 1985 to 2026
$55.0M
NCI NIH HHS P30 CA036727
6 · The paper itself

Abstract

backgroundMYC amplification or overexpression is common in Group 3 medulloblastoma and is associated with the worst prognosis. Recently, protein arginine methyl transferase (PRMT) 5 expression has been closely associated with aberrant MYC function in various cancers, including brain tumors such as glioblastoma. However, the role of PRMT5 and its association with MYC in medulloblastoma have not been explored. Here, we report the role of PRMT5 as a novel regulator of MYC and implicate PRMT5 as a potential therapeutic target in MYC-driven medulloblastoma.

methodsExpression and association between PRMT5 and MYC in primary medulloblastoma tumors were investigated using publicly available databases. Expression levels of PRMT5 protein were also examined using medulloblastoma cell lines and primary tumors by western blotting and immunohistochemistry, respectively. Using MYC-driven medulloblastoma cells, we examined the physical interaction between PRMT5 and MYC by co-immunoprecipitation and co-localization experiments. To determine the functional role of PRMT5 in MYC-driven medulloblastoma, PRMT5 was knocked-down in MYC-amplified cells using siRNA and the consequences of knockdown on cell growth and MYC expression/stability were investigated. In vitro therapeutic potential of PRMT5 in medulloblastoma was also evaluated using a small molecule inhibitor, EPZ015666.

resultsWe observed overexpression of PRMT5 in MYC-driven primary medulloblastoma tumors and cell lines compared to non-MYC medulloblastoma tumors and adjacent normal tissues. We also found that high expression of PRMT5 is inversely correlated with patient survival. Knockdown of PRMT5 using siRNA in MYC-driven medulloblastoma cells significantly decreased cell growth and MYC expression. Mechanistically, we found that PRMT5 physically associated with MYC by direct protein-protein interaction. In addition, a cycloheximide chase experiment showed that PRMT5 post-translationally regulated MYC stability. In the context of therapeutics, we observed dose-dependent efficacy of PRMT5 inhibitor EPZ015666 in suppressing cell growth and inducing apoptosis in MYC-driven medulloblastoma cells. Further, the expression levels of PRMT5 and MYC protein were downregulated upon EPZ015666 treatment. We also observed a superior efficacy of this inhibitor against MYC-amplified medulloblastoma cells compared to non-MYC-amplified medulloblastoma cells, indicating specificity.

conclusionOur results reveal the regulation of MYC oncoprotein by PRMT5 and suggest that targeting PRMT5 could be a potential therapeutic strategy for MYC-driven medulloblastoma.

Indexed as

ApoptosisCell CycleCell Line, TumorCell ProliferationCell SurvivalCerebellar NeoplasmsHumansIsoquinolinesMedulloblastomaProtein-Arginine N-MethyltransferasesProtein BindingProto-Oncogene Proteins c-mycPyrimidinesRNA InterferenceSurvival AnalysisGSK3235025IsoquinolinesMYC protein, humanPRMT5 protein, humanProtein-Arginine N-MethyltransferasesProto-Oncogene Proteins c-mycPyrimidinesMedulloblastomaMYC proteinPRMT5PRMT5 inhibitor

Identifiers

PMID31694585
PMCPMC6836472
OpenAlexW2986588740

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.