[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-380490-105":59,"doc-detail-380490-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","epigenomic-perturbation-of-novel-egfr-enhancers-reduces-the-proliferative-and-invasive-capacity-of-glioblastoma-and-increases-sensitivity-to-temozolomide","Epigenomic perturbation of novel EGFR enhancers reduces the proliferative and invasive capacity of glioblastoma and increases sensitivity to temozolomide","","Glioblastoma is an aggressive primary brain tumour with limited treatment options and a median survival of about 14 months. Although EGFR alterations are frequent, EGFR-targeted therapies have not delivered clear clinical benefits. This study investigates how EGFR regulatory-genome organization and novel EGFR enhancer elements affect glioblastoma cells. CRISPR/Cas9 enhancer perturbation decreases EGFR expression, reduces proliferation and invasion, shifts metabolism toward mitochondrial respiration, increases apoptosis, and enhances temozolomide sensitivity. The findings support enhancer-driven control of key cancer-gene programs to improve TMZ efficacy.",{"@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/epigenomic-perturbation-of-novel-egfr-enhancers-reduces-the-proliferative-and-invasive-capacity-of-glioblastoma-and-increases-sensitivity-to-temozolomide/380490/",{"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/epigenomic-perturbation-of-novel-egfr-enhancers-reduces-the-proliferative-and-invasive-capacity-of-glioblastoma-and-increases-sensitivity-to-temozolomide/380490.png","ImageObject",300,407,{"name":92,"@type":93},"Pentious","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main research question of the study?","Question",{"text":112,"@type":113},"The study examines how perturbing the EGFR regulatory genome, specifically novel EGFR enhancers near a glioblastoma-associated SNP, affects glioblastoma cell behavior and treatment response.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were the EGFR enhancer regions manipulated?",{"text":117,"@type":113},"CRISPR/Cas9-based approaches were used to target EGFR enhancer regions, generating multiple modified glioblastoma cell lines for functional analysis.",{"name":119,"@type":110,"acceptedAnswer":120},"What effects does enhancer perturbation have on glioblastoma cells and therapy sensitivity?",{"text":121,"@type":113},"Epigenomic perturbation reduces EGFR expression and lowers proliferative and invasive capacity, accompanied by metabolic reprogramming toward mitochondrial respiration and increased apoptosis. It also increases sensitivity to temozolomide.","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},380490,1790899455,{"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":34,"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},1374404730887,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","Vincent et al. BMC Cancer (2023) 23:945 [https://doi.org/10.1186/s12885-023-11418-9](https://doi.org/10.1186/s12885-023-11418-9)  \nBMC Cancer  \n RESEARCH Open Access  \nEpigenomic perturbation of novel EGFR  \nenhancers reduces the proliferative and invasive capacity of glioblastoma and increases sensitivity to temozolomide  \nCraig A. Vincent 1,2, Itzel Nissen 1,2, Soran Dakhel 1,2, Andreas Hörnblad 1 and Silvia Remeseiro 1,2*  \nAbstract  \nBackground Glioblastoma (GB) is the most aggressive of all primary brain tumours and due to its highly invasive nature, surgical resection is nearly impossible. Patients typically rely on radiotherapy with concurrent temozolomide (TMZ) treatment and face a median survival of ~ 14 months. Alterations in the Epidermal Growth Factor Receptor gene (EGFR) are common in GB tumours, but therapies targeting EGFR have not shown significant clinical efficacy. Methods Here, we investigated the influence of the EGFR regulatory genome on GB cells and identified novel EGFR enhancers located near the GB-associated SNP rs723527 . We used CRISPR/Cas9-based approaches to target the EGFR enhancer regions, generating multiple modified GB cell lines, which enabled us to study the functional response to enhancer perturbation.  \nResults Epigenomic perturbation of the EGFR regulatory region decreases EGFR expression and reduces the proliferative and invasive capacity of glioblastoma cells, which also undergo a metabolic reprogramming in favour of mitochondrial respiration and present increased apoptosis. Moreover, EGFR enhancer-perturbation increases the sensitivity of GB cells to TMZ, the first-choice chemotherapeutic agent to treat glioblastoma.  \nConclusions Our findings demonstrate how epigenomic perturbation of EGFR enhancers can ameliorate the aggressiveness of glioblastoma cells and enhance the efficacy ofTMZ treatment. This study demonstrates how CRISPR/ Cas9-based perturbation of enhancers can be used to modulate the expression of key cancer genes, which can help improve the effectiveness of existing cancer treatments and potentially the prognosis of difficult-to-treat cancers such as glioblastoma.  \nKeywords EGFR, Enhancer, Glioblastoma, Epigenomic perturbation, CRISPR/Cas9  \n*Correspondence: Silvia Remeseiro  \nsilvia. remeseiro@umu.se  \n1 Umeå Centre for Molecular Medicine (UCMM), Umeå University, Umeå, Sweden  \n2 Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, Umeå, Sweden  \nIntroduction  \nGlioblastoma (GB), also known as grade 4 astrocytoma, is a common and highly aggressive type of primary brain tumour, for which survival rates have not significantly improved in recent decades (median survival ~ 14 months, 5-year survival \u003C 5%) [1, 2]. Due to its highly invasive nature, complete surgical resection is nearly impossible [3] and therefore recurrence is inevitable. While the addition of tumour-treating  \n© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[. The Creative Commons Public Domain Dedication waiver (](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public ","cbCaiblVuzKxVADj","https://ap.wps.com/l/cbCaiblVuzKxVADj","pdf",3765428,14,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction","[{\"question\":\"What is the main research question of the study?\",\"answer\":\"The study examines how perturbing the EGFR regulatory genome, specifically novel EGFR enhancers near a glioblastoma-associated SNP, affects glioblastoma cell behavior and treatment response.\"},{\"question\":\"How were the EGFR enhancer regions manipulated?\",\"answer\":\"CRISPR/Cas9-based approaches were used to target EGFR enhancer regions, generating multiple modified glioblastoma cell lines for functional analysis.\"},{\"question\":\"What effects does enhancer perturbation have on glioblastoma cells and therapy sensitivity?\",\"answer\":\"Epigenomic perturbation reduces EGFR expression and lowers proliferative and invasive capacity, accompanied by metabolic reprogramming toward mitochondrial respiration and increased apoptosis. It also increases sensitivity to temozolomide.\"}]","Epigenomic perturbation of novel EGFR enhancers reduces the proliferative and invasive capacity of glioblastoma and increases sensitivity to temozolomide | PDF",1790240411,35]