[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-355924-105":59,"doc-detail-355924-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","zranb1-depletion-inhibits-neuroblastoma-progression-by-destabilizing-mycn-through-ezh2-mediated-deubiquitination","ZRANB1 depletion inhibits neuroblastoma progression by destabilizing MYCN through EZH2-mediated deubiquitination","","Background: Neuroblastoma (NB) is a frequent pediatric malignant solid tumor, with especially aggressive behavior in MYCN-amplified cases. Developing targeted therapies depends on clarifying molecular mechanisms driving NB progression. ZRANB1, a deubiquitinating enzyme implicated in multiple cancers, remains insufficiently defined in NB. Methods: Transcriptomic bioinformatic analyses and functional experiments in NB cells and xenograft models test how ZRANB1 affects the EZH2–MYCN axis and tumor phenotypes.",{"@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":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/zranb1-depletion-inhibits-neuroblastoma-progression-by-destabilizing-mycn-through-ezh2-mediated-deubiquitination/355924/",{"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/zranb1-depletion-inhibits-neuroblastoma-progression-by-destabilizing-mycn-through-ezh2-mediated-deubiquitination/355924.png","ImageObject",300,407,{"name":92,"@type":93},"Franzy","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the central finding about ZRANB1 in MYCN-amplified neuroblastoma?","Question",{"text":112,"@type":113},"ZRANB1 depletion suppresses neuroblastoma progression, and the study links ZRANB1 to MYCN regulation via EZH2-mediated deubiquitination and stabilization-related mechanisms.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were potential MYCN-dependent genes and the ZRANB1 mechanism evaluated?",{"text":117,"@type":113},"The work uses transcriptomic bioinformatic analyses of datasets (GSE85047 and GSE80149) and then tests ZRANB1 effects in NB cells using proliferation, migration, invasion, and tumor sphere assays, supported by biochemical interaction and ubiquitination experiments.",{"name":119,"@type":110,"acceptedAnswer":120},"Why does the EZH2–MYCN regulatory axis matter for therapeutic targeting?",{"text":121,"@type":113},"MYCN is a key driver in high-risk NB and is linked to poor outcomes; establishing a ZRANB1–EZH2–MYCN regulatory axis highlights ZRANB1 as a promising target to indirectly maintain or disrupt MYCN stability in MYCN-amplified disease.","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},355924,1790174203,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"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":36},2336478945519,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","Cell Biol Toxicol (2026) 42:80  \n[https://doi.org/10.1007/s10565-026-10186-z](https://doi.org/10.1007/s10565-026-10186-z)  \nZRANB1 depletion inhibits neuroblastoma progression by destabilizing MYCN through EZH2‑mediated deubiquitination  \nZhichao Wang · Long Cheng · Guanghui Li · Huiyan Cheng  \nReceived: 27 September 2025 / Accepted: 31 March 2026 © The Author(s) 2026  \nAbstract  \nBackground Neuroblastoma (NB) is a common malignant solid tumor in children, notably aggressive in cases with MYCN amplification. Unraveling the mechanisms behind NB progression is crucial for developing targeted therapies. ZRANB1, a deubiquitinating enzyme, has emerged as a significant player in many cancers, but its specific function in NB still tobe fully elucidated.  \nMethods Bioinformatic analyses of transcriptomic datasets (GSE85047 and GSE80149) were performed to identify potential MYCN-dependent prosurvival genes. The biological functions of ZRANB1  \nSupplementary Information The online version contains supplementary material available at [https://doi](https://doi). org/10.1007/s10565-026-10186-z.  \nZ. Wang  \nDepartment of Pediatric Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin, China  \nL. Cheng  \nDepartment of Intensive Care Unit, The First Hospital of Jilin University, Changchun 130021, Jilin, China  \nG. Li  \nDepartment of Vascular Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin, China  \nH. Cheng (*)  \nDepartment of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun 130021, Jilin, China  \ne-mail: [chenghuiyan@jlu.edu.cn](chenghuiyan@jlu.edu.cn)  \nin NB cells were assessed by CCK-8, colony formation, migration, invasion, and tumor sphere formation assays. Co-IP, Western blot, CHX chase, and ubiquitination assays were performed to assess the regulatory relationship among ZRANB1, EZH2, and MYCN. Catalytically inactive ZRANB1 mutant and in vitro pull-down assays were performed to validate the requirement of deubiquitinase activity and direct interactions. We evaluated the contribution of the ZRANB1-EZH2-MYCN axis to tumor growth using cell-based assays and mouse xenograft models. Results ZARNB1 was substantially higher in MYCN-amplified BE(2)M17 cell lines. Functional studies demonstrated that ZRANB1 promoted proliferation, migration, and tumorigenicity. Mechanistically, although ZRANB1 did not directly bind MYCN, it formed a ternary complex with EZH2 and MYCN, thereby stabilizing MYCN via EZH2-mediated regulation. Deubiquitinase activity was required for ZRANB1-mediated MYCN stabilization, and direct ZRANB1-EZH2 interaction was confirmed by in vitro pull-down assays.  \nConclusions This study identifies ZRANB1 asan upstream deubiquitinase that stabilizes EZH2, thereby indirectly maintaining MYCN stability in MYCN-amplified neuroblastoma. These findings establish a ZRANB1-EZH2-MYCN regulatory axis and highlight ZRANB1 as a promising therapeutic target in MYCN-amplified NB.  \nKeywords ZRANB1 · MYCN · EZH2 · Ubiquitination · Neuroblastoma  \nIntroduction  \nNeuroblastoma (NB), a neural crest-derived tumor, is the most common extracranial solid tumor in children (Quintás et al. 2020) . NB exhibits highly variable biological and clinical behaviors, from spontaneous regression to aggressive, treatmentresistant metastases involving multiple organs. These variations are partially due to specific genetic alterations (Qiu & Matthay 2022) . The current treatment strategies for NB involve a combination of approaches tailored to the patient’s specific risk category, including surgical resection, radiotherapy, chemotherapy, stem cell transplantation, and clinical trials (Chung et al. 2021) . Due to the genetic, morphological, and clinical heterogeneity properties that NB exhibited (Zafar et al. 2021), those treatments for NB are still limited by significant side effects, development of drug resistance, incomplete tumor resection, and long-term health sequelae, underscoring the necess","cbCairnYMLEMiATz","https://ap.wps.com/l/cbCairnYMLEMiATz","pdf",12213583,16,"English","# Abstract\n# Introduction\n# Methods and Results\n# Conclusions","[{\"question\":\"What is the central finding about ZRANB1 in MYCN-amplified neuroblastoma?\",\"answer\":\"ZRANB1 depletion suppresses neuroblastoma progression, and the study links ZRANB1 to MYCN regulation via EZH2-mediated deubiquitination and stabilization-related mechanisms.\"},{\"question\":\"How were potential MYCN-dependent genes and the ZRANB1 mechanism evaluated?\",\"answer\":\"The work uses transcriptomic bioinformatic analyses of datasets (GSE85047 and GSE80149) and then tests ZRANB1 effects in NB cells using proliferation, migration, invasion, and tumor sphere assays, supported by biochemical interaction and ubiquitination experiments.\"},{\"question\":\"Why does the EZH2–MYCN regulatory axis matter for therapeutic targeting?\",\"answer\":\"MYCN is a key driver in high-risk NB and is linked to poor outcomes; establishing a ZRANB1–EZH2–MYCN regulatory axis highlights ZRANB1 as a promising target to indirectly maintain or disrupt MYCN stability in MYCN-amplified disease.\"}]","ZRANB1 depletion inhibits neuroblastoma progression by destabilizing MYCN through EZH2-mediated deubiquitination | PDF",1790121783]