Fiche publication
Date publication
septembre 2026
Journal
NAR cancer
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MOTORINE Iouri
,
Dr MARCHAND Virginie
Tous les auteurs :
Briones-Martin-Del-Campo M, Lee AG, Dinh T, Marchand V, Motorin Y, Román M, Bi Q, Leung SG, Horlbeck MA, Sayles LC, Seong BKA, Gilbert L, Stegmaier K, Sweet-Cordero EA
Lien Pubmed
Résumé
Over 90% of Ewing sarcomas (EWS) are driven by the EWS-FLI1 fusion oncoprotein. EWS-FLI1 acts as a pioneer transcription factor, altering the expression of hundreds of genes including many long non-coding RNAs (lncRNAs). The role of these lncRNAs in the oncogenesis of EWS is mostly unknown. We developed a CRISPR interference (CRISPRi) strategy to knock down expression of lncRNA loci expressed in EWS and evaluate their effect on proliferation and tumor growth . While most lncRNA knockdown had minimal effect on cell proliferation, selective inhibition of SNHG1, SNHG12, and SNHG30 significantly reduced both proliferation of Ewing cells and the growth of Ewing tumors . These results were validated by individual knockdown followed by RNA-seq to assess their functional impact. We observed a decrease in post-transcriptional modifications (2'-O-methylation and pseudouridylation) at specific rRNA positions known to be guided by snoRNAs encoded in SNHG1 and SNHG12. Collectively, we demonstrate that expression of SNHG1, SNHG12, and SNHG30 in EWS cells contributes to the maintenance of cancer cell fitness via their role in intron-processed snoRNA genes. Thus, post-transcriptional regulation of rRNA may be a previously underappreciated consequence of EWS-FLI1 expression.
Mots clés
Humans, Sarcoma, Ewing, genetics, RNA, Small Nucleolar, genetics, RNA, Long Noncoding, genetics, Introns, genetics, Animals, Cell Line, Tumor, Cell Proliferation, genetics, RNA-Binding Protein EWS, genetics, Oncogene Proteins, Fusion, genetics, Gene Expression Regulation, Neoplastic, Proto-Oncogene Protein c-fli-1, genetics, Mice, Bone Neoplasms, genetics, Gene Knockdown Techniques, RNA Processing, Post-Transcriptional
Référence
NAR Cancer. 2026 09;8(3):zcag019
