Evidence map›Paper›PMID 40664627›Full record

ArticleNature communications2025

Subversion of mRNA degradation pathways by EWSR1::FLI1 represents a therapeutic vulnerability in Ewing sarcoma.

Bartimée Galvan, Loïc Ongena, Jonathan Bruyr, Gregory Fettweis, Eva Lucarelli, Arnaud Lavergne, Emeline Mariavelle, Tina M O'Grady, Zahrat El Oula Hassoun, Margaux Claes and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. 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
–field-weighted citation impact
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.

  1. Review
  2. Article
  3. Review
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  5. Article
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

25 authors.

Bartimée GalvanLaboratory of Gene Expression and Cancer, GIGA Institute, University of Liège (ULiège), Liège, Belgium.ORCID http://orcid.org/0000-0001-8629-4860
Loïc OngenaLaboratory of Gene Expression and Cancer, GIGA Institute, University of Liège (ULiège), Liège, Belgium.ORCID http://orcid.org/0000-0002-7768-1428
Jonathan BruyrLaboratory of Gene Expression and Cancer, GIGA Institute, University of Liège (ULiège), Liège, Belgium.
Gregory FettweisLaboratory of Gene Expression and Cancer, GIGA Institute, University of Liège (ULiège), Liège, Belgium.ORCID http://orcid.org/0000-0002-6623-2264
Eva LucarelliLaboratory of Gene Expression and Cancer, GIGA Institute, University of Liège (ULiège), Liège, Belgium.
Arnaud LavergneGenomics Platform, GIGA Institute, University of Liège (ULiège), Liège, Belgium.ORCID http://orcid.org/0000-0003-4817-3202
Emeline MariavelleLaboratory of Gene Expression and Cancer, GIGA Institute, University of Liège (ULiège), Liège, Belgium.
Tina M O'GradyLaboratory of Gene Expression and Cancer, GIGA Institute, University of Liège (ULiège), Liège, Belgium.ORCID http://orcid.org/0000-0002-1283-0293
Zahrat El Oula HassounLaboratory of Gene Expression and Cancer, GIGA Institute, University of Liège (ULiège), Liège, Belgium.ORCID http://orcid.org/0000-0001-6125-2867
Margaux ClaesLaboratory of Gene Expression and Cancer, GIGA Institute, University of Liège (ULiège), Liège, Belgium.
Laurence DuboisLaboratory of Gene Expression and Cancer, GIGA Institute, University of Liège (ULiège), Liège, Belgium.
Kevin A W LeeDivision of Life Science, The Hong Kong University of Sci. & Tech, Clear Water Bay, Kowloon, Hong Kong SAR, China.
Véronique KruysLaboratory of Molecular Biology of the Gene, Department of Molecular Biology, Free University of Brussels (ULB), 6041, Gosselies, Belgium.
Cyril GueydanLaboratory of Molecular Biology of the Gene, Department of Molecular Biology, Free University of Brussels (ULB), 6041, Gosselies, Belgium.
Jules DurandUniversité Franche-Comté, INSERM, EFS BFC, UMR1098, « Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique », F-25000, Besançon, France.
Eric HervouetUniversité Franche-Comté, INSERM, EFS BFC, UMR1098, « Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique », F-25000, Besançon, France.ORCID http://orcid.org/0000-0002-4841-7812
Florian H GeyerHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Ana BanitoHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0003-2188-0003
Roland ImleHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0001-9564-6952
Lianghao MaoHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Ashok K JayaveluHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-3292-1117
Thomas G P GrünewaldHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0003-0920-7377
Florencia Cidre-AranazHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-0246-7179
Jean-Claude TwizereLaboratory of Viral Interactomes Networks, GIGA Institute, University of Liège (ULiège), 4000, Liège, Belgium.ORCID http://orcid.org/0000-0002-8683-705X
Franck DequiedtLaboratory of Gene Expression and Cancer, GIGA Institute, University of Liège (ULiège), Liège, Belgium. fdequiedt@uliege.be.ORCID http://orcid.org/0000-0003-1234-7477

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Many cancers are defined by gene fusions that frequently encode oncogenic transcription factors (TFs), such as EWSR1::FLI1 in Ewing sarcoma (EwS). Here, we report that independently to its canonical roles in transcription, EWSR1::FLI1 also functions as an mRNA decay factor, reshaping mRNA stability in EwS. This function participates in EWSR1::FLI1 tumorigenicity and involves interactions of EWSR1::FLI1 with the CCR4-NOT deadenylation complex via its EWSR1-derived low-complexity domain and with the RNA-binding protein HuR/ELAVL1 via its FLI1-derived region. Strikingly, we find that EWSR1::FLI1-mediated mRNA decay antagonizes the normal mRNA protective function of HuR and renders EwS cells highly sensitive to HuR inhibition. Our findings uncover a post-transcriptional function of EWSR1::FLI1 and suggest that targeting mRNA stability mechanisms may offer therapeutic opportunities for EwS.

Indexed as

Bone NeoplasmsProto-Oncogene Protein c-fli-1RNA-Binding Protein EWSRNA StabilitySarcoma, EwingAnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansMiceOncogene Proteins, FusionRNA-Binding ProteinsRNA, MessengerEWSR1 protein, humanFLI1 protein, humanOncogene Proteins, FusionProto-Oncogene Protein c-fli-1RNA-Binding Protein EWSRNA-Binding ProteinsRNA, Messenger

Identifiers

PMID40664627
PMCPMC12263829

What OpenQuestion holds

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Registered trials

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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.