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In neuroblastoma, elevated PRMT5 and E2F1 is associated with poor prognosis high-risk disease and correlates with amplified MYCN. MYCN promotes splicing factor gene expression; with PRMT5 and E2F1, this yields a deregulated alternative RNA splicing program that blocks apoptosis. Inhibition of PRMT5 or E2F1 inactivation restores normal splicing and sensitizes cells to apoptosis.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/sustained-cancer-relevant-alternative-rna-splicing-events-driven-by-prmt5-in-high-risk-neuroblastoma/332990/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/sustained-cancer-relevant-alternative-rna-splicing-events-driven-by-prmt5-in-high-risk-neuroblastoma/332990.png","ImageObject",300,407,{"name":92,"@type":93},"Valentina","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-25","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the role of PRMT5 and E2F1 in high-risk neuroblastoma?","Question",{"text":112,"@type":113},"The article reports that PRMT5 and E2F1 are elevated in poor prognosis high-risk neuroblastoma and correlate with amplified MYCN, linking them to an oncogenic regulatory program.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does MYCN influence alternative RNA splicing in neuroblastoma?",{"text":117,"@type":113},"MYCN drives expression of splicing factor genes. Together with PRMT5 and E2F1, this produces a deregulated alternative RNA splicing program.",{"name":119,"@type":110,"acceptedAnswer":120},"How do inhibiting PRMT5 or inactivating E2F1 affect apoptosis?",{"text":121,"@type":113},"PRMT5 inhibition or E2F1 inactivation restores normal splicing and sensitizes neuroblastoma cells to apoptosis, countering the apoptosis-impeding splicing program.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},332990,1790189801,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},13056703020460,"https://ap-avatar.wpscdn.com/avatar/be000253dac470eee5d?_k=1778207105932848923","Sustained cancer-relevant alternative RNA splicing events driven by PRMT5 in high-risk neuroblastoma  \nLaurel Tabe Bate-Eya 1, Gulsah Albayrak 1, Simon Mark Carr 1, Amit Shrestha 1, Alexander Kanapin2, Anastasia Samsonova2 and Nicholas Barrie La Thangue 1   \n1 Laboratory of Cancer Biology, Department of Oncology, University of Oxford, UK  \n2 Institute of Translational Biomedicine, Saint Petersburg State University, Russia  \nKeywords  \nalternative RNA splicing; apoptosis; E2F1; neuroblastoma; PRMT5; therapeutic target  \nCorrespondence  \nN. B. La Thangue, Laboratory of Cancer Biology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK  \nE-mail: [nick.lathangue@oncology.ox.ac.uk](nick.lathangue@oncology.ox.ac.uk)  \nGulsah Albayrak and Simon Mark Carr contributed equally to this article  \n(Received 7 March 2024, revised 12 June 2024, accepted 8 July 2024, available online 17 July 2024)  \ndoi:10 . 1002/1878-0261 .13702  \nProtein arginine methyltransferase 5 (PRMT5) is over-expressed in a wide variety of cancers and is implicated as having a key oncogenic role, achieved in part through its control of the master transcription regulator E2F1 . We investigated the relevance of PRMT5 and E2F1 in neuroblastoma (NB) and found that elevated expression of PRMT5 and E2F1 occurs in poor prognosis high-risk disease and correlates with an amplified Myelocytomatosis viral-related oncogene, neuroblastoma-derived (MYCN) gene. Our results show that MYCN drives the expression of splicing factor genes that, together with PRMT5 and E2F1, lead to a deregulated alternative RNA splicing programme that impedes apoptosis. Pharmacological inhibition of PRMT5 or inactivation of E2F1 restores normal splicing and renders NB cells sensitive to apoptosis. Our findings suggest that a sustained cancer-relevant alternative RNA splicing programme desensitises NB cells to apoptosis, and identify PRMT5 as a potential therapeutic target for high-risk disease.  \n1. Introduction  \nNeuroblastoma is the most common extracranial solid tumour in children and is associated with significant morbidity and mortality [1] . The disease exhibits phenotypic heterogeneity and is broadly divided into poor prognosis high-risk and improved prognosis lower-risk disease [2], and metastatic drug-resistant disease is a major clinical challenge [3] . One of the major obstacles in developing new treatment modalities is the limited understanding of the biologically relevant cancer  \npathways that drive the malignant phenotype [2] . A variety of somatic mutations in oncogenic pathways have been described, for example, amplification of the MYCN gene and mutation in the ALK and ATRX genes [4–7] MYCN gene amplification occurs in about 25% of tumours and is a common feature of high-risk disease, with rapid disease progression and poor prognosis; abnormal MYCN expression is the strongest predictor of poor prognosis [8] . In contrast, germline  \nAbbreviations  \nACIN1, apoptotic chromatin condenser inducer 1; CFLAR, CASP8 and FADD like apoptosis regulator; ChIP, chromatin immunoprecipitation; Cr, CRISPR; DEGs, differentially expressed genes; E2F1, E2 promoter binding factor 1; FACS, flourescence activated cell sorting; GEO, Gene Expression Omnibus; GFP, green fluorescence protein; GO, Gene Ontology; HA, Haemagglutinin; INSS, international neuroblastoma staging system; KEGG, Kyoto Encyclopedia of Genes and Genomes; MTT, 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide; MYCN, myelocytomatosis viral-related oncogene, neuroblastoma derived; NB, neuroblastoma; ORF, open reading frame; OS, overall survival; pRb, retinoblastoma protein; PRMT5, protein arginine methyltransferase 5; PSI, per cent spliced in; rMATS, replicate multivariate analysis of transcript splicing; TARGET, therapeutically applicable research to generate effective treatments; TCGA, The Cancer Genome Atlas; Vst, variance stabilising transformation; WT, wild type.  \nMolecular Oncology 19","cbCaiiMx3mVTZVvW","https://ap.wps.com/l/cbCaiiMx3mVTZVvW","pdf",3139770,23,"English","# Introduction\n## Background on neuroblastoma risk groups and mutations\n## Role of E2F1 and PRMT5 in gene regulation and splicing\n## Link between methylation and splicing machinery","[{\"question\":\"What is the role of PRMT5 and E2F1 in high-risk neuroblastoma?\",\"answer\":\"The article reports that PRMT5 and E2F1 are elevated in poor prognosis high-risk neuroblastoma and correlate with amplified MYCN, linking them to an oncogenic regulatory program.\"},{\"question\":\"How does MYCN influence alternative RNA splicing in neuroblastoma?\",\"answer\":\"MYCN drives expression of splicing factor genes. Together with PRMT5 and E2F1, this produces a deregulated alternative RNA splicing program.\"},{\"question\":\"How do inhibiting PRMT5 or inactivating E2F1 affect apoptosis?\",\"answer\":\"PRMT5 inhibition or E2F1 inactivation restores normal splicing and sensitizes neuroblastoma cells to apoptosis, countering the apoptosis-impeding splicing program.\"}]","Sustained cancer-relevant alternative RNA splicing events driven by PRMT5 in high-risk neuroblastoma | PDF",1790000305,58]