Evidence map›Paper›PMID 23435416›Full record

ArticleOncogene2014

JARID2 is a direct target of the PAX3-FOXO1 fusion protein and inhibits myogenic differentiation of rhabdomyosarcoma cells.

Z S Walters, B Villarejo-Balcells, D Olmos, T W S Buist, E Missiaglia, R Allen, B Al-Lazikani, M D Garrett, J Blagg, J Shipley

Open access · greenAbstract read
In one paragraph

Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

62 citing papers in PubMed, 105 citations in OpenAlex.

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  11. Polycomb Repressive Complex 2 in Oncology.Cancer treatment and research · 2023
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  12. Critical Roles of Polycomb Repressive Complexes in Transcription and Cancer.International journal of molecular sciences · 2022
    Review
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2 more citing papers are in PubMed but not listed here.

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

10 authors at 2 institutions in 1 country.

Z S WaltersSarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, London, UK.
B Villarejo-BalcellsSarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, London, UK.
D Olmos1] Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, London, UK [2] Sarcoma Unit, Royal Marsden Hospital NHS Trust, London, UK.
T W S Buist1] Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, London, UK [2] Computational Biology and Chemogenomics, Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, Institute of Cancer Research, Sutton, London, UK.
E Missiaglia1] Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, London, UK [2] Swiss Institute of Bioinformatics, Bioinformatics Core Facility, University of Lausanne, Lausanne, Switzerland.
R AllenSarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, London, UK.
B Al-LazikaniComputational Biology and Chemogenomics, Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, Institute of Cancer Research, Sutton, London, UK.
M D GarrettCell Cycle Control Team, Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, London, UK.
J BlaggMedicinal Chemistry, Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, London, UK.
J ShipleySarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, London, UK.
Institute of Cancer Research · GBCancer Research UK · GB

Funding

Cancer Research UK 11566Cancer Research UK A10399Cancer Research UK C5066/A10399Medical Research Council
6 · The paper itself

Abstract

Rhabdomyosarcomas (RMS) are the most frequent soft-tissue sarcoma in children and characteristically show features of developing skeletal muscle. The alveolar subtype is frequently associated with a PAX3-FOXO1 fusion protein that is known to contribute to the undifferentiated myogenic phenotype of RMS cells. Histone methylation of lysine residues controls developmental processes in both normal and malignant cell contexts. Here we show that JARID2, which encodes a protein known to recruit various complexes with histone-methylating activity to their target genes, is significantly overexpressed in RMS with PAX3-FOXO1 compared with the fusion gene-negative RMS (t-test; P < 0.0001). Multivariate analyses showed that higher JARID2 levels are also associated with metastases at diagnosis, independent of fusion gene status and RMS subtype (n = 120; P = 0.039). JARID2 levels were altered by silencing or overexpressing PAX3-FOXO1 in RMS cell lines with and without the fusion gene, respectively. Consistent with this, we demonstrated that JARID2 is a direct transcriptional target of the PAX3-FOXO1 fusion protein. Silencing JARID2 resulted in reduced cell proliferation coupled with myogenic differentiation, including increased expression of Myogenin (MYOG) and Myosin Light Chain (MYL1) in RMS cell lines representative of both the alveolar and embryonal subtypes. Induced myogenic differentiation was associated with a decrease in JARID2 levels and this phenotype could be rescued by overexpressing JARID2. Furthermore, we that showed JARID2 binds to and alters the methylation status of histone H3 lysine 27 in the promoter regions of MYOG and MYL1 and that the interaction of JARID2 at these promoters is dependent on EED, a core component of the polycomb repressive complex 2 (PRC2). Therefore, JARID2 is a downstream effector of PAX3-FOXO1 that maintains an undifferentiated myogenic phenotype that is characteristic of RMS. JARID2 and other components of PRC2 may represent novel therapeutic targets for treating RMS patients.

Indexed as

Cell DifferentiationCell Line, TumorCell ProliferationEnhancer of Zeste Homolog 2 ProteinGene Expression Regulation, NeoplasticHistone DemethylasesHumansMuscle DevelopmentMyogeninNuclear ProteinsOncogene Proteins, FusionPaired Box Transcription FactorsPolycomb Repressive Complex 2Promoter Regions, GeneticPromyelocytic Leukemia ProteinRhabdomyosarcomaEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanHistone DemethylasesJARID2 protein, humanMyogeninNuclear ProteinsOncogene Proteins, FusionPaired Box Transcription FactorsPAX3-FOXO1A fusion protein, humanPML protein, humanPolycomb Repressive Complex 2Promyelocytic Leukemia ProteinTranscription FactorsTumor Suppressor Proteins

Identifiers

PMID23435416
PMCPMC3982124
OpenAlexW2033407338

What OpenQuestion holds

Textmetadata
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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.