[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-381830-105":59,"doc-detail-381830-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","b7h3-increases-ferroptosis-resistance-by-inhibiting-cholesterol-metabolism-in-colorectal-cancer","B7H3 increases ferroptosis resistance by inhibiting cholesterol metabolism in colorectal cancer","","Ferroptosis, a regulated form of cell death, has been linked to multiple cancers, including colorectal cancer (CRC), yet its molecular basis remains insufficiently defined. This study identifies B7H3 as a regulator of ferroptosis resistance in CRC. B7H3 knockdown sensitizes CRC cells to ferroptosis, whereas B7H3 overexpression enhances resistance, reflected by ferroptosis gene expression and key ferroptosis indicators. Mechanistically, B7H3 promotes resistance through AKT-dependent suppression of SREBP2-mediated cholesterol metabolism; cholesterol supplementation and SREBP2 inhibition reverse the effect, and multiplex immunohistochemistry associates B7H3 with CRC prognosis.",{"@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/b7h3-increases-ferroptosis-resistance-by-inhibiting-cholesterol-metabolism-in-colorectal-cancer/381830/",{"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/b7h3-increases-ferroptosis-resistance-by-inhibiting-cholesterol-metabolism-in-colorectal-cancer/381830.png","ImageObject",300,407,{"name":92,"@type":93},"Elsa","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-25","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does B7H3 play in ferroptosis in colorectal cancer cells?","Question",{"text":112,"@type":113},"B7H3 functions as a regulator of ferroptosis resistance. Knockdown decreases, while overexpression increases ferroptosis resistance in CRC cells.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does B7H3 influence cholesterol metabolism during ferroptosis regulation?",{"text":117,"@type":113},"B7H3 promotes ferroptosis resistance by regulating SREBP2-mediated cholesterol metabolism, and it downregulates SREBP2 through activation of the AKT pathway.",{"name":119,"@type":110,"acceptedAnswer":120},"What evidence links the B7H3 pathway to clinical outcomes in CRC?",{"text":121,"@type":113},"Multiplex immunohistochemistry shows B7H3, PTGS2, and SREBP2 expression in CRC tumor tissues, and their expression is associated with patient prognosis.","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},381830,1790319019,{"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":29,"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":41},137455077381,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","Received: 24 April 2023 | Revised: 17 July 2023 | Accepted: 14 August 2023  \nDOI: 10. 1111/cas.15944  \nOR I G I NAL ART I C L E  \nB7H3 increases ferroptosis resistance by inhibiting cholesterol metabolism in colorectal cancer  \nHaiyan Jin1,2 | Mengxin Zhu3 | Dongze Zhang1,2 | Xiaoshan Liu4  | Yuesheng Guo4 | Lu Xia3 | Yanjun Chen3 | Yuqi Chen1,3 | Ruyan Xu1,2 | Cuiping Liu1,2 | Qinhua Xi1,3 | Suhua Xia2,5 | Tongguo Shi1,2  | Guangbo Zhang1,2  \n1Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, China 2Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou, China  \n3 Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China 4Pasteurien College, Suzhou Medical College, Soochow University, Suzhou, China  \n5Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China  \nCorrespondence  \nGuangbo Zhang and Tongguo Shi, Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 178 East Ganjiang Road, Suzhou 215000, China.  \nEmail: [15962265210@163.com](15962265210@163.com:)[:](15962265210@163.com:) shitg@ [suda.edu.cn](suda.edu.cn)  \nSuhua Xia, Department of Oncology, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou 215000, China. [Email:](Email: xiasuhua@suda.edu.cn)[ xiasuhua@suda.edu.cn](Email: xiasuhua@suda.edu.cn)  \nFunding information  \nGusu Talent Project of Suzhou, Grant/ Award Number: SGSWS2020011; Jiangsu Provincial Medical Key Discipline, Grant/ Award Number: ZDXK202246; Natural Science Foundation Project of the Doctoral Cultivation Program, Grant/ Award Number: BXQN202119; Suzhou“Science and Education Revitalize Health”Youth Science and Technology Project, Grant/Award Number: KJXW2022005; Suzhou Natural Science Foundation, Grant/Award Number: sky2022046 and sky2022128; the key project of Jiangsu Provincial Health and wellness  \nAbstract  \nFerroptosis, a newly discovered form of regulated cell death, has been reported tobe associated with multiple cancers, including colorectal cancer (CRC) . However, the underlying molecular mechanism is still unclear. In this study, we identified B7H3 asa potential regulator of ferroptosis resistance in CRC. B7H3 knockdown decreased but B7H3 overexpression increased the ferroptosis resistance of CRC cells, as evidenced by the expression of ferroptosis-associated genes (PTGS2, FTL, FTH, and GPX4) and the levels of important indicators of ferroptosis (malondialdehyde, iron load) . Moreover, B7H3 promoted ferroptosis resistance by regulating sterol regulatory element binding protein 2 (SREBP2)-mediated cholesterol metabolism. Both exogenous cholesterol supplementation and treatment with the SREBP2 inhibitor betulin reversed the effect of B7H3 on ferroptosis in CRC cells. Furthermore, we verified that B7H3 downregulated SREBP2 expression by activating the AKT pathway. Additionally, multiplex immunohistochemistry was carried out to show the expression of B7H3, prostaglandin-endoperoxide synthase 2, and SREBP2 in CRC tumor tissues, which was associated with the prognosis of patients with CRC. In summary, our findings reveal a role for B7H3 in regulating ferroptosis by controlling cholesterol metabolism in CRC.  \nAbbreviations: CRC, colorectal cancer; DEG, differentially expressed gene; FTH, ferritin heavy chain; FTL, ferritin light chain; GO, Gene Ontology; GPX4, glutathione peroxidase 4; GSH, glutathione; HMGCR, 3-hydroxy-3-methylglutaryl-CoA reductase; HMGCS, 3-hydroxy-3-methylglutaryl-CoA synthase; HO-1, heme oxygenase-1; IHC, immunohistochemistry; LDL-C, low-density lipoprotein cholesterol; LDLR, low-density lipoprotein receptor; MDA, malondialdehyde; mIHC, multiplex immunohistochemistry; NC, negative control; Nrf2, nuclear factor erythroid 2-related factor 2; n-SREBP2, nuclear SREBP2; PTGS2, prostaglandin-endoperoxide synthase 2; qPCR, quantitative PCR; RCD, regulated cell death; RNA-seq,","cbCaioJx8nzCltvI","https://ap.wps.com/l/cbCaioJx8nzCltvI","pdf",16450165,12,"English","# Introduction\n## Ferroptosis and colorectal cancer context\n# Abstract\n## B7H3 as a regulator of ferroptosis resistance\n## Mechanism via SREBP2 and cholesterol metabolism","[{\"question\":\"What role does B7H3 play in ferroptosis in colorectal cancer cells?\",\"answer\":\"B7H3 functions as a regulator of ferroptosis resistance. Knockdown decreases, while overexpression increases ferroptosis resistance in CRC cells.\"},{\"question\":\"How does B7H3 influence cholesterol metabolism during ferroptosis regulation?\",\"answer\":\"B7H3 promotes ferroptosis resistance by regulating SREBP2-mediated cholesterol metabolism, and it downregulates SREBP2 through activation of the AKT pathway.\"},{\"question\":\"What evidence links the B7H3 pathway to clinical outcomes in CRC?\",\"answer\":\"Multiplex immunohistochemistry shows B7H3, PTGS2, and SREBP2 expression in CRC tumor tissues, and their expression is associated with patient prognosis.\"}]","B7H3 increases ferroptosis resistance by inhibiting cholesterol metabolism in colorectal cancer | PDF",1790247338]