[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-376359-105":59,"doc-detail-376359-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","setd5-in-glioma-cells-conferred-trail-resistance-induction","SETD5 in glioma cells conferred TRAIL resistance induction","","Glioblastoma is highly aggressive and frequently resists conventional therapies, and TRAIL-induced apoptosis remains hindered by TRAIL resistance. This study evaluates how SETD5 modulates TRAIL resistance in GBM by integrating public multi-omics datasets for expression, mutation, and promoter methylation, and by analyzing clinical and immune associations. In U87 and LN229 cells, SETD5 knockdown enhances TRAIL-mediated apoptosis, suppresses survival pathways, and reduces deubiquitinase expression.",{"@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/setd5-in-glioma-cells-conferred-trail-resistance-induction/376359/",{"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/setd5-in-glioma-cells-conferred-trail-resistance-induction/376359.png","ImageObject",300,407,{"name":92,"@type":93},"Fans","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-27","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What problem does the study address in glioblastoma treatment?","Question",{"text":112,"@type":113},"Glioblastoma shows poor prognosis partly because tumors resist conventional therapies, and TRAIL resistance limits the effectiveness of TRAIL-based apoptosis induction.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was SETD5 investigated in relation to TRAIL resistance?",{"text":117,"@type":113},"The study assessed SETD5 expression, mutation, and promoter methylation using public datasets, then tested functional effects by siRNA knockdown of SETD5 followed by TRAIL treatment in U87 and LN229 cell lines.",{"name":119,"@type":110,"acceptedAnswer":120},"What happens to TRAIL-induced apoptosis when SETD5 is knocked down?",{"text":121,"@type":113},"SETD5 depletion enhances TRAIL-mediated apoptosis, reduces survival markers such as p-AKT, P-ERK, and NF-κB, and increases pro-apoptotic proteins including Cytochrome c and SMAC.","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},376359,1790537698,{"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":14,"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},5909892330395,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \nSETD5 in glioma cells conferred TRAIL resistance induction  \nLakshay Taneja, Sachin Bhardwaj & Ajay KumarYadav􀀍  \nGlioblastoma (GBM) is the most aggressive and lethal form of primary brain tumor, often characterized by resistance to conventional therapies and a poor clinical prognosis. Tumor Necrosis FactorRelated Apoptosis-Inducing Ligand (TRAIL) selectively induces apoptosis in cancer cells; however, TRAIL resistance remains a significant obstacle inGBM treatment. SETD5, a histone methyl transferase with emerging roles in chromatin remodeling and gene regulation, has been implicated in neurodevelopmental disorders and cancer, but remains poorly characterized in glioma biology.  \nThis study investigates the role of SETD5 in modulating TRAIL resistance and explores its potential as a therapeutic target in GBM. Publicly available datasets (TCGA, GTEx, GEPIA2, UALCAN, Gliovis, and GSCA) were used to assess SETD5 expression, mutation, and promoter methylation inGBM. Associations with clinical parameters, molecular subtypes, immune infiltration, and functional states were analyzed using tools like cBioPortal, CancerSEA, MEXPRESS, and STRING. siRNA-mediated knockdown of SETD5 was performed in U87 and LN229 GBM cell lines, followed by TRAIL treatment. Western blotting assessed changes in apoptotic and survival pathways, while wound healing assays evaluated cell migration. Expression of deubiquitinases (USP5, USP8, and USP10) was also measured. SETD5 was significantly upregulated in GBM compared to normal brain tissues across multiple databases and was especially elevated in the Mesenchymal and Classical subtypes. CNV analyses revealed alterations in SETD5 that correlated with immunosuppressive cell infiltration. SETD5 expression was positively correlated with survival pathways and negatively correlated with cytotoxic immune infiltration. TRAIL treatment induced SETD5 expression in a dose-dependent manner. Knockdown of SETD5 enhanced TRAIL-mediated apoptosis, reduced expression of survival markers (p-AKT, P-ERK, NF-κB), and increased pro-apoptotic proteins (Cytochrome c, SMAC) . SETD5 depletion also downregulated USP5, USP8, and USP10, suggesting its role in stabilizing oncogenic proteins via deubiquitination. SETD5 plays a critical role in promoting TRAIL resistance and GBM survival by regulating apoptotic pathways, immune evasion, and deubiquitinase expression. Moreover knockdown of SETD along with TRAIL treatment leads to down regulation NFκB which a major promoter for cell survival. Its inhibition sensitizes glioma cells to TRAIL-induced apoptosis, identifying SETD5 as a potential therapeutic target. Targeting SETD5 could represent a novel strategy to overcome TRAIL resistance and enhance the efficacy of GBM therapies.  \nKeywords SETD5, TRAIL, NFKB, Apoptosis  \nAbbreviations  \nGBM Glioblastoma multiforme  \nSETD5 Su(var)3–9, Enhancer of Zeste, and Trithorax Domain-Containing 5 TRAIL Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand NFκB Nuclear factor kappa B  \nDUB Deubiquinating enzymes USP Ubiquitin specific protease  \nGlioblastoma, a highly aggressive and malignant brain tumor, remains a significant challenge in clinical oncology due to its resistance to conventional therapies and poor prognosis1. Despite advances in surgical resection, radiation, and chemotherapy, glioma cells often exhibit remarkable resistance to treatment, leading to recurrence and patient mortality.  \nMolecular Cancer Genetics and Signal Transduction laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, North Campus, Gate No. 1, Vishwavidyalaya Marg, Mall Road, 44, AH2, New Delhi 110007, India. 􀀍 email: [ayadav@acbr.du.ac.in](ayadav@acbr.du.ac.in); [ajayacbrdu@gmail.com](ajayacbrdu@gmail.com); [ajay9774@gmail.com](ajay9774@gmail.com)  \n[www. nature.com/scientificreports/](www. nature.com/scientificreports/)  \nTumor Necrosis Factor-Related Apop","cbCaioD3DWQfNxrm","https://ap.wps.com/l/cbCaioD3DWQfNxrm","pdf",1981071,13,"English","# Study overview\n## Background on GBM and TRAIL resistance\n## Role of SETD5\n# Bioinformatics analyses\n## Expression, mutation, and methylation across datasets\n## Clinical, molecular subtype, and immune infiltration associations\n# Experimental validation\n## siRNA knockdown and TRAIL treatment in GBM cell lines\n## Apoptotic and survival signaling assessment\n## Migration and deubiquitinase expression evaluation\n# Mechanistic implications and therapeutic outlook","[{\"question\":\"What problem does the study address in glioblastoma treatment?\",\"answer\":\"Glioblastoma shows poor prognosis partly because tumors resist conventional therapies, and TRAIL resistance limits the effectiveness of TRAIL-based apoptosis induction.\"},{\"question\":\"How was SETD5 investigated in relation to TRAIL resistance?\",\"answer\":\"The study assessed SETD5 expression, mutation, and promoter methylation using public datasets, then tested functional effects by siRNA knockdown of SETD5 followed by TRAIL treatment in U87 and LN229 cell lines.\"},{\"question\":\"What happens to TRAIL-induced apoptosis when SETD5 is knocked down?\",\"answer\":\"SETD5 depletion enhances TRAIL-mediated apoptosis, reduces survival markers such as p-AKT, P-ERK, and NF-κB, and increases pro-apoptotic proteins including Cytochrome c and SMAC.\"}]","SETD5 in glioma cells conferred TRAIL resistance induction | PDF",1790218362,33]