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This study identifies CRB2 as an epigenetic modulator of ferroptosis in head and neck squamous cell carcinoma (HNSCC). CRB2 expression associates with ferroptosis-related genes and improved patient prognosis. Ferroptosis inducers erastin and RSL3 increase CRB2, and CRB2 overexpression sensitizes HNSCC to ferroptosis, suppressing growth in vitro and in vivo. Mechanistically, CRB2 promotes histone H4 lysine 20 dimethylation at the SLC7A11 promoter by disrupting LSD1(E8A)-USP7 interaction, epigenetically inhibiting transcription and driving ferroptosis.",{"@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/crb2-activates-an-epigenetic-axis-to-promote-ferroptosis-in-head-and-neck-squamous-cell-carcinoma/416278/",{"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/crb2-activates-an-epigenetic-axis-to-promote-ferroptosis-in-head-and-neck-squamous-cell-carcinoma/416278.png","ImageObject",300,407,{"name":92,"@type":93},"Stanford","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What role does CRB2 play in ferroptosis in HNSCC?","Question",{"text":113,"@type":114},"CRB2 functions as an epigenetic modulator of ferroptosis in head and neck squamous cell carcinoma. Its expression correlates with ferroptosis-related genes and better patient prognosis, and increasing CRB2 sensitizes cells to ferroptosis.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How do erastin and RSL3 affect CRB2 and ferroptosis?",{"text":118,"@type":114},"Ferroptosis inducers erastin and RSL3 significantly increase CRB2 expression. This supports ferroptosis activation and enhances ferroptosis-related responses in HNSCC.",{"name":120,"@type":111,"acceptedAnswer":121},"What epigenetic mechanism links CRB2 to ferroptosis induction?",{"text":122,"@type":114},"CRB2 increases dimethylation of histone H4 lysine 20 at the SLC7A11 promoter, epigenetically inhibiting its transcription. It does so by hindering the interaction between LSD1(E8A) and USP7, facilitating degradation of LSD1(E8A) and promoting ferroptosis.","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},416278,1790811999,{"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":146,"preview_page_count":4},2336477552062,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","CRB2 Activates an Epigenetic Axis to Promote Ferroptosis in Head and Neck Squamous Cell Carcinoma  \nDiekuo Zhang1,2,3, Junli Hu1,2,3, Gangcai Zhu1,2,3, Chao Liu1,2,3, Guo Li1,2,3, Shanhong Lu1,2,3, Huihong Chen1,2,3, Xueying Wang1,2,3, Zongnan Yu1,2,3, Helei Yan1,2,3, Yaodong Ding1,2,3, Xin Zhang1,2,3,4, Junwei Hou1,5, Yuanzheng Qiu1,2,3,4, Mien-Chie Hung6,7, Zhaoyi Lu1,2,3, and Yong Liu1,2,3,4  \n|  |  | A |  | B | S |  | T | R |  | A |  | C | T |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |\n| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |\n|  | Therapeutic activation of ferroptosis is a potential strategy to induce cell death in cancer. Deciphering the epigenetic regulation offerroptosis could provide insights into effective approaches for enhancing ferroptosis in cancer cells. In this study, we identified CRB2 as an epigenetic modulator of ferroptosis in head and necksquamous cell carcinoma (HNSCC). CRB2 expression correlated with the expression of ferroptosis-related genes and improved prognosis in patients with HNSCC. Ferroptosis inducers erastin and RSL3 significantly increased CRB2 expression, and overexpression of CRB2 sensitized HNSCC to ferroptosis, suppressing growth in vitro and in vivo. CRB2 upregulation led to an increase in the dimethylation of histone H4 lysine 20 in the promoter region of the ferroptosis inhibitor SLC7A11, which epigenetically inhibited its\u003Cbr>􀀶 |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | transcription and induced ferroptosis in HNSCC. Mechanistically, CRB2 hindered the interaction between the E8A isoform of the histone lysine demethylase LSD1 and the deubiquitinase USP7, thereby facilitating the degradation of LSD1(E8A) and subsequently increasing histone H4 lysine 20 dimethylation levels. Taken together, these results indicate that CRB2 stimulates ferroptosis by activating an epigenetic axis, suggesting that the upregulation of CRB2 is a potential therapeutic strategy for HNSCC.\u003Cbr>Significance: CRB2 epigenetically inhibits SCL7A11-GPX4 signaling to promote ferroptosis and suppress tumor growth in head and neck squamous cell carcinoma, providing insights that could guide ferroptosis-activating treatment approaches. |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |\n\nIntroduction  \nHead and neck tumors are common upper respiratory tract neoplasms that are closely associated with excessive consumption of tobacco and alcohol; approximately 90% of cases are pathologically diagnosed as head and neck squamous cell carcinoma (HNSCC) . Despite sustained improvements in surgery-oriented therapies  \n1Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, China. 2Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, China. 3Clinical Research Center for Laryngopharyngeal and Voice Disorders in Hunan Province, Changsha, China. 4National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), Changsha, China. 5Center for Molecular Oncology and Immunology, Xiangya Hospit","cbCaic2RYRaqqbBz","https://ap.wps.com/l/cbCaic2RYRaqqbBz","pdf",24867217,15,"English","# Introduction\n## Background on HNSCC and treatment challenges\n## Rationale for epigenetic regulation of ferroptosis\n## Study focus on CRB2 and ferroptosis","[{\"question\":\"What role does CRB2 play in ferroptosis in HNSCC?\",\"answer\":\"CRB2 functions as an epigenetic modulator of ferroptosis in head and neck squamous cell carcinoma. Its expression correlates with ferroptosis-related genes and better patient prognosis, and increasing CRB2 sensitizes cells to ferroptosis.\"},{\"question\":\"How do erastin and RSL3 affect CRB2 and ferroptosis?\",\"answer\":\"Ferroptosis inducers erastin and RSL3 significantly increase CRB2 expression. This supports ferroptosis activation and enhances ferroptosis-related responses in HNSCC.\"},{\"question\":\"What epigenetic mechanism links CRB2 to ferroptosis induction?\",\"answer\":\"CRB2 increases dimethylation of histone H4 lysine 20 at the SLC7A11 promoter, epigenetically inhibiting its transcription. It does so by hindering the interaction between LSD1(E8A) and USP7, facilitating degradation of LSD1(E8A) and promoting ferroptosis.\"}]","CRB2 Activates an Epigenetic Axis to Promote Ferroptosis in Head and Neck Squamous Cell Carcinoma | PDF",1790604844,38]