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000302857 1001_ $$00000-0001-8629-4860$$aGalvan, Bartimée$$b0
000302857 245__ $$aSubversion of mRNA degradation pathways by EWSR1::FLI1 represents a therapeutic vulnerability in Ewing sarcoma.
000302857 260__ $$a[London]$$bSpringer Nature$$c2025
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000302857 520__ $$aMany 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.
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000302857 650_7 $$2NLM Chemicals$$aProto-Oncogene Protein c-fli-1
000302857 650_7 $$2NLM Chemicals$$aEWSR1 protein, human
000302857 650_7 $$2NLM Chemicals$$aRNA-Binding Protein EWS
000302857 650_7 $$2NLM Chemicals$$aFLI1 protein, human
000302857 650_7 $$2NLM Chemicals$$aOncogene Proteins, Fusion
000302857 650_7 $$2NLM Chemicals$$aRNA, Messenger
000302857 650_7 $$2NLM Chemicals$$aRNA-Binding Proteins
000302857 650_2 $$2MeSH$$aSarcoma, Ewing: genetics
000302857 650_2 $$2MeSH$$aSarcoma, Ewing: metabolism
000302857 650_2 $$2MeSH$$aSarcoma, Ewing: pathology
000302857 650_2 $$2MeSH$$aHumans
000302857 650_2 $$2MeSH$$aProto-Oncogene Protein c-fli-1: metabolism
000302857 650_2 $$2MeSH$$aProto-Oncogene Protein c-fli-1: genetics
000302857 650_2 $$2MeSH$$aRNA Stability: genetics
000302857 650_2 $$2MeSH$$aRNA-Binding Protein EWS: metabolism
000302857 650_2 $$2MeSH$$aRNA-Binding Protein EWS: genetics
000302857 650_2 $$2MeSH$$aCell Line, Tumor
000302857 650_2 $$2MeSH$$aAnimals
000302857 650_2 $$2MeSH$$aOncogene Proteins, Fusion: metabolism
000302857 650_2 $$2MeSH$$aOncogene Proteins, Fusion: genetics
000302857 650_2 $$2MeSH$$aMice
000302857 650_2 $$2MeSH$$aRNA, Messenger: metabolism
000302857 650_2 $$2MeSH$$aRNA, Messenger: genetics
000302857 650_2 $$2MeSH$$aRNA-Binding Proteins: metabolism
000302857 650_2 $$2MeSH$$aRNA-Binding Proteins: genetics
000302857 650_2 $$2MeSH$$aGene Expression Regulation, Neoplastic
000302857 650_2 $$2MeSH$$aBone Neoplasms: genetics
000302857 650_2 $$2MeSH$$aBone Neoplasms: metabolism
000302857 7001_ $$00000-0002-7768-1428$$aOngena, Loïc$$b1
000302857 7001_ $$aBruyr, Jonathan$$b2
000302857 7001_ $$00000-0002-6623-2264$$aFettweis, Gregory$$b3
000302857 7001_ $$aLucarelli, Eva$$b4
000302857 7001_ $$00000-0003-4817-3202$$aLavergne, Arnaud$$b5
000302857 7001_ $$aMariavelle, Emeline$$b6
000302857 7001_ $$00000-0002-1283-0293$$aO'Grady, Tina M$$b7
000302857 7001_ $$00000-0001-6125-2867$$aHassoun, Zahrat El Oula$$b8
000302857 7001_ $$aClaes, Margaux$$b9
000302857 7001_ $$aDubois, Laurence$$b10
000302857 7001_ $$aLee, Kevin A W$$b11
000302857 7001_ $$aKruys, Véronique$$b12
000302857 7001_ $$aGueydan, Cyril$$b13
000302857 7001_ $$aDurand, Jules$$b14
000302857 7001_ $$00000-0002-4841-7812$$aHervouet, Eric$$b15
000302857 7001_ $$0P:(DE-He78)824510670ec489266e6e294c4f8b0e6c$$aGeyer, Florian$$b16$$udkfz
000302857 7001_ $$0P:(DE-He78)990de6ec6c2f0a40b17ed75162ca19e8$$aBanito, Ana$$b17$$udkfz
000302857 7001_ $$0P:(DE-He78)3c021852cf94cb29825e65baa82ed54b$$aImle, Roland$$b18$$udkfz
000302857 7001_ $$aMao, Lianghao$$b19
000302857 7001_ $$aJayavelu, Ashok K$$b20
000302857 7001_ $$0P:(DE-He78)7a590ab95c6f7ba52880452da78ecd6c$$aGrünewald, Thomas$$b21$$udkfz
000302857 7001_ $$00000-0002-0246-7179$$aCidre-Aranaz, Florencia$$b22
000302857 7001_ $$00000-0002-8683-705X$$aTwizere, Jean-Claude$$b23
000302857 7001_ $$00000-0003-1234-7477$$aDequiedt, Franck$$b24
000302857 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-025-61725-x$$gVol. 16, no. 1, p. 6537$$n1$$p6537$$tNature Communications$$v16$$x2041-1723$$y2025
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