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This work focuses on MYCN, a key genomic alteration in neuroblastoma, and its downstream effects on disease evolution. An integrative computational workflow analyzes published genomics datasets to assess how MYCN amplification enhances metabolism-related transcription factor (TF) gene upregulation. Results highlight overexpressed TFs and their enrichment in metabolic cellular processes via gene ontology and literature curation, and mechanistic validation through omics-based analysis of MYCN-amplified and MYCN-enforced ChIP-seq datasets.",{"@graph":69,"@context":123},[70,84,106],{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/mycn-amplifications-and-metabolic-rewiring-in-neuroblastoma/381745/",{"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/mycn-amplifications-and-metabolic-rewiring-in-neuroblastoma/381745.png","ImageObject",300,407,{"name":92,"@type":93},"supergirl","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is the main focus of the article on neuroblastoma?","Question",{"text":113,"@type":114},"The article investigates how MYCN amplification reshapes neuroblastoma by upregulating metabolism-related transcription factor (TF) genes and revealing MYCN’s regulatory connections to these factors.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How do the authors study MYCN’s impact in the work?",{"text":118,"@type":114},"They use an integrative computational workflow on published genomics datasets and extend it with omics-based computational analyses of relevant ChIP-seq data.",{"name":120,"@type":111,"acceptedAnswer":121},"What evidence supports that many metabolism-related TFs are MYCN targets?",{"text":122,"@type":114},"The study reports direct MYCN binding across regulatory sequences near multiple upregulated TF genes, supported by cistromic computational assessments and validation from the mechanistic ChIP-seq analyses.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},381745,1790834714,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":26},962088121634,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","cancers   \nArticle  \nMYCN Amplifications and Metabolic Rewiring in Neuroblastoma  \nMarialena Pouliou 1,†, Marianna A. Koutsi 1,†, Lydia Champezou 1, Angeliki-Ioanna Giannopoulou 2, Giannis Vatsellas 1, Christina Piperi 2, * and Marios Agelopoulos 1, *  \nCitation: Pouliou, M.; Koutsi, M.A.; Champezou, L.; Giannopoulou, A.-I.; Vatsellas, G.; Piperi, C.; Agelopoulos, M. MYCN Amplifications and Metabolic Rewiring in Neuroblastoma. Cancers 2023, 15, 4803. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cancers15194803  \nAcademic Editor: David Wong  \nReceived: 5 September 2023  \nRevised: 20 September 2023  \nAccepted: 27 September 2023  \nPublished: 29 September 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Center of Basic Research, Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou St., 11527 Athens, Greece; [mpouliou@bioacademy.gr](mpouliou@bioacademy.gr) (M.P.); [mkoutsi@bioacademy.gr](mkoutsi@bioacademy.gr) (M.A.K.); [lchamp@bioacademy.gr](lchamp@bioacademy.gr) (L.C.); [gvatsellas@bioacademy.gr](gvatsellas@bioacademy.gr) (G.V.)  \n2 Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 M. Asias Street Bldg 16, 11527 Athens, Greece; [angelig@med.uoa.gr](angelig@med.uoa.gr)  \n* Correspondence: [cpiperi@med.uoa.gr](cpiperi@med.uoa.gr) (C.P.); [magelo@bioacademy.gr](magelo@bioacademy.gr) (M.A.);  \nTel.: +30-2107462610 (C.P.); +30-2106597454 (M.A.); Fax: +30-2106597545 (M.A.)† These authors contributed equally to this work.  \nSimple Summary: Transcription factors (TFs) can reprogram cellular states by modulating the expression of their target genes and establishing gene expression programs under homeostasis and diseases manifestation. In neuroblastoma, the TF MYCN has been recorded as dysregulated, presenting both aberrant expression and genomic abnormalities across its coding locus. Herein, we computationally investigated the gene expression characteristics that distinguish neuroblastomaMYCN-amplified from neuroblastoma non-MYCN-amplified cancer cells, and we addressed the upregulation of several metabolism-related TF-encoding genes. Moreover, cistromic computational assessments of MYCN revealed its direct binding across regulatory sequences that reside in cis proximity to several of those genes. These results illuminate substantial mechanistic interrelationships between the key driver of neuroblastoma and a wealth of transcriptional regulators in cancer cells.  \nAbstract: Cancer is a disease caused by (epi)genomic and gene expression abnormalities and characterized by metabolic phenotypes that are substantially different from the normal phenotypes of the tissues of origin. Metabolic reprogramming is one of the key features of tumors, including those established in the human nervous system. In this work, we emphasize a well-known cancerous genomic alteration: the amplification of MYCN and its downstream effects in neuroblastoma phenotype evolution. Herein, we extend our previous computational biology investigations by conducting an integrative workflow applied to published genomics datasets and comprehensively assess the impact of MYCN amplification in the upregulation of metabolism-related transcription factor (TF)-encoding genes in neuroblastoma cells. The results obtained first emphasized overexpressed TFs, and subsequently those committed in metabolic cellular processes, as validated by gene ontology analyses (GOs) and literature curation. Several genes encoding for those TFs were investigated at the mechanistic and regulatory levels by conducting further omics-based computational biology assessments applied on published ","cbCaicIOwqEqrgp8","https://ap.wps.com/l/cbCaicIOwqEqrgp8","pdf",5234312,24,"English","# Introduction\n## Cancer metabolism and metabolic reprogramming\n# Abstract\n## MYCN amplification and downstream regulatory effects\n## Integrative computational workflow and validation\n# Keywords\n## Study focus areas","[{\"question\":\"What is the main focus of the article on neuroblastoma?\",\"answer\":\"The article investigates how MYCN amplification reshapes neuroblastoma by upregulating metabolism-related transcription factor (TF) genes and revealing MYCN’s regulatory connections to these factors.\"},{\"question\":\"How do the authors study MYCN’s impact in the work?\",\"answer\":\"They use an integrative computational workflow on published genomics datasets and extend it with omics-based computational analyses of relevant ChIP-seq data.\"},{\"question\":\"What evidence supports that many metabolism-related TFs are MYCN targets?\",\"answer\":\"The study reports direct MYCN binding across regulatory sequences near multiple upregulated TF genes, supported by cistromic computational assessments and validation from the mechanistic ChIP-seq analyses.\"}]","MYCN Amplifications and Metabolic Rewiring in Neuroblastoma | PDF",1790246856]