[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-450305-105":3,"detail-sidebar-cat-0-en-105":80,"doc-detail-450305-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":73,"head_meta":75,"extra_data":77,"updated_unix":79},105,"en","fto-mediated-m6a-demethylation-of-csf3-suppresses-netosis-via-downregulation-of-rln2-expression-in-colorectal-cancer","FTO-mediated m6A demethylation of CSF3 suppresses NETosis via downregulation of RLN2 expression in colorectal cancer","","CSF3 drives colorectal cancer progression, and N6-methyladenosine (m6A) modification is identified as a key regulator of RNA effects in cancer cells, yet the mechanism linking CSF3, m6A, and colorectal cancer pathogenesis remains unclear. Using neutrophil isolation and assays of purity and survival, colorectal cancer is modeled with AOM/DSS. Loss- and gain-of-function experiments test CSF3 control of NETosis and tumorigenesis, while FTO-mediated m6A demethylation is examined for its impact on tumor growth and NET formation, alongside RLN2-dependent rescue. ",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/fto-mediated-m6a-demethylation-of-csf3-suppresses-netosis-via-downregulation-of-rln2-expression-in-colorectal-cancer/450305/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/fto-mediated-m6a-demethylation-of-csf3-suppresses-netosis-via-downregulation-of-rln2-expression-in-colorectal-cancer/450305.png","ImageObject",300,407,{"name":42,"@type":43},"Genevieve","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-04","2026-09-30",true,{"@type":52,"interactionType":53,"userInteractionCount":30},"InteractionCounter",{"@type":54},"ViewAction",{"@type":56,"mainEntity":57},"FAQPage",[58,64,68],{"name":59,"@type":60,"acceptedAnswer":61},"What role does CSF3 play in colorectal cancer progression?","Question",{"text":62,"@type":63},"CSF3 is described as exerting a significant function in colorectal cancer progression, with CSF3 levels linked to NETosis and tumorigenesis in the study’s experiments.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"How is NETosis connected to the study’s CSF3 axis?",{"text":67,"@type":63},"The text states that CSF3 influences NETosis: CSF3 overexpression enhances NETosis, while CSF3 knockdown suppresses NETosis, and RLN2 supplementation can rescue the NETosis phenotype after CSF3 loss.",{"name":69,"@type":60,"acceptedAnswer":70},"What is the proposed mechanism involving FTO and RLN2?",{"text":71,"@type":63},"Mechanistically, FTO-mediated m6A demethylation of CSF3 mRNA suppresses colorectal cancer tumorigenesis in vivo. CSF3 upregulation counteracts FTO’s tumor-suppressive effects, with RLN2 expression acting as the downstream factor driving NETosis and tumor behavior.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},450305,1790790643,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":88,"show_sort_weight":89,"slug":90},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":92,"show_sort_weight":93,"slug":94},"Exam",70,"exam",{"id":96,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},5,"Comic",60,"comic",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},6,"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},7,"Healthcare",40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},8,30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":96,"slug":129},19,"General","general",{"code":4,"msg":81,"data":131},{"doc_id":78,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":111,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":30,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},1374391974585,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Cell Biol Toxicol (2026) 42:4  \n[https://doi.org/10.1007/s10565-025-10120-9](https://doi.org/10.1007/s10565-025-10120-9)  \nFTO‑mediated m6A demethylation of CSF3 suppresses NETosis via downregulation of RLN2 expression in colorectal cancer  \nJunfeng Xu · Jie Zhang · Ruoran Li · Shengxin Chen · Changwei Duan · Xianzong Ma · Xuexin Wang · Xinyan Liu · Lingyun Gu · Ke Meng ·  \nMingyang Li  \nReceived: 19 June 2025 / Accepted: 6 November 2025  \n© The Author(s) 2025  \nAbstract CSF3 exerts a significant function in the progression of colorectal cancer (CRC). N6-methyladenosine (m6A) modification is now considered the main driving factor of RNA influence for maintaining homeostasis in cancer cells. Nevertheless, how m6A mediates the role of CSF3 and its influence in pathogenesis of CRC is still elusive. After neutrophil isolation from bone marrow, the purity and survival rate of neutrophils were assessed. Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) was employed to construct the CRC  \n\n| Junfeng Xu, Jie Zhang, and Ruoran Li contributed equally to this work. |\n| --- |\n| Highlights\u003Cbr>• FTO-mediated m6A demethylation regulates CSF3 mRNA, suppressing NETosis and tumorigenesis.\u003Cbr>• CSF3-triggered upregulation of relaxin-2 (RLN2) rescues NETosis in CSF3-deficient CRC cells co-cultured with neutrophils, revealing a druggable axis.\u003Cbr>• CSF3, FTO, and RLN2 could be served as the potential biomarkers for CRC. |\n| Supplementary Information The online version contains supplementary material available at [https://doi](https://doi). org/10.1007/s10565-025-10120-9. |\n\nJ. Xu · S. Chen · C. Duan · X. Ma · X. Wang · X. Liu ·  \nK. Meng (*) · M. Li (*)  \nSenior Department of Gastroenterology, Chinese PLA General Hospital, Beijing 100853, China [e-mail: mengke301@126.com](e-mail: mengke301@126.com)  \nM. Li  \n[e-mail: mingyangli_pla@163.com](e-mail: mingyangli_pla@163.com)  \nmice model. Both loss-of-function and gain-of-function experiments were conducted to explore the influence of CSF3 on NETosis and tumorigenesis of CRC in vitro and in vivo. The purity and survival rate of neutrophils were 88.07% and 94.84%, respectively. Overexpression of CSF3 (oe-CSF3) markedly enhanced NETosis, while CSF3 knockdown (sh-CSF3) suppressed it. Intriguingly, CSF3 expression positively correlated with relaxin-2 (RLN2) levels in CRC cells, and RLN2 supplementation rescued tumorigenesis and NETosis after sh-CSF3 treatment. Mechanistically, fat mass and obesity-associated protein (FTO)-mediated m6A demethylation of CSF3 mRNA suppressed CRC tumorigenesis in vivo. CSF3 upregulation counteracted the tumor-suppressive effects of FTO overexpression, restoring NETosis and tumor growth. Consistent with this, FTO overexpression in CRC mice alleviated disease severity, as evidenced by improved body weight, reduced tumor burden, and diminished NETosis. Collectively, our findings establish a novel regulatory axis in which FTO-dependent m6Ademethylation ofCSF3 suppresses NETosis by inhibiting RLN2 expression, offering new insights into therapeutic targeting of the m6A-CSF3-RLN2 pathway in CRC.  \nJ. Zhang  \nDepartment of Gastroenterology, The Seventh Medical Center of Chinese, PLA General Hospital, Beijing 100700, China  \nR. Li · S. Chen · C. Duan · X. Wang · X. Liu Graduate School, Chinese PLA General Hospital, Beijing 100853, China  \nKeywords Colorectal cancer ·  \nN6-methyladenosine · FTO · CSF3 · RLN2 · NETosis  \nIntroduction  \nColorectal cancer (CRC) is one of the most popular cancers worldwide, with probably 1.9 million new cases and nearly 900000 deaths annually (Andrei et al. 2022; Siegel et al. 2024) . The conventional treatment for CRC includes surgery, radiotherapy, chemotherapy, and immunotherapy (Ganesh et al. 2019) . Although CRC has improved in screening and treatment, its incidence rate, prevalence and mortality are still high, especially for patients diagnosed with advanced CRC, and the 5-year survival rate is below 10%(Schmitt and Greten 2021) . Thus, it’s imperativ","cbCaietPOZUS11wu","https://ap.wps.com/l/cbCaietPOZUS11wu","pdf",8810381,17,"English","# Highlights\n# Supplementary Information\n# Keywords\n# Introduction","[{\"question\":\"What role does CSF3 play in colorectal cancer progression?\",\"answer\":\"CSF3 is described as exerting a significant function in colorectal cancer progression, with CSF3 levels linked to NETosis and tumorigenesis in the study’s experiments.\"},{\"question\":\"How is NETosis connected to the study’s CSF3 axis?\",\"answer\":\"The text states that CSF3 influences NETosis: CSF3 overexpression enhances NETosis, while CSF3 knockdown suppresses NETosis, and RLN2 supplementation can rescue the NETosis phenotype after CSF3 loss.\"},{\"question\":\"What is the proposed mechanism involving FTO and RLN2?\",\"answer\":\"Mechanistically, FTO-mediated m6A demethylation of CSF3 mRNA suppresses colorectal cancer tumorigenesis in vivo. CSF3 upregulation counteracts FTO’s tumor-suppressive effects, with RLN2 expression acting as the downstream factor driving NETosis and tumor behavior.\"}]","FTO-mediated m6A demethylation of CSF3 suppresses NETosis via downregulation of RLN2 expression in colorectal cancer | PDF",1790732837,43]