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This study investigates FTO, the first identified m6A RNA demethylase, and its role in GC tumorigenesis and progression. FTO is markedly upregulated in GC tissues and cells, correlating with nerve invasion, tumor size, lymph node metastasis, and worse patient prognosis. Functionally, FTO enhances GC cell viability, colony formation, migration, and invasion. Mechanistically, FTO regulates the SP1-AURKB-ATM pathway, driving signaling events via phosphorylation and dephosphorylation changes in key proteins, supporting FTO as a potential diagnostic biomarker.",{"@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/rna-demethylase-fto-participates-in-malignant-progression-of-gastric-cancer-by-regulating-sp1-aurkb-atm-pathway/332189/",{"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/rna-demethylase-fto-participates-in-malignant-progression-of-gastric-cancer-by-regulating-sp1-aurkb-atm-pathway/332189.png","ImageObject",300,407,{"name":92,"@type":93},"Maeve","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-26","2026-09-21",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 biological focus of the study in gastric cancer?","Question",{"text":112,"@type":113},"The study focuses on the RNA demethylase FTO and how it contributes to gastric cancer tumorigenesis and progression through downstream signaling mechanisms.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does FTO expression relate to clinical outcomes in gastric cancer?",{"text":117,"@type":113},"FTO is upregulated in malignant gastric tissues and its higher expression is associated with adverse prognosis, including worse survival measures and correlations with advanced invasion and metastasis parameters.",{"name":119,"@type":110,"acceptedAnswer":120},"What signaling pathway does the study propose for FTO-driven progression?",{"text":121,"@type":113},"The study proposes that FTO promotes gastric cancer progression by regulating the SP1-AURKB-ATM pathway, affecting phosphorylation and dephosphorylation of key proteins involved in the process.","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},332189,1790460337,{"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":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,"preview_page_count":4},5909877438554,"https://ap-avatar.wpscdn.com/avatar/5600025385ad2bf12a7?_k=1778553567797529272","communications biology Article  \n\n| \u003Cbr>[https://doi.org/10.1038/s42003-024-06477-y](https://doi.org/10.1038/s42003-024-06477-y) |  |\n| --- | --- |\n| RNA demethylaseFTO participates in malignant progression ofgastric cancer by regulating SP1-AURKB-ATM pathway\u003Cbr> Check for updates |  |\n| Xueliang Zeng1,2,4, Yao Lu1,3,4, Taohui Zeng2, Wenyu Liu2, Weicai Huang2, Tingting Yu2, Xuerui Tang2, Panpan Huang2, Bei Li 2  & Hulai Wei 1  |  |\n| Gastric cancer (GC) is the 5th most prevalent cancer and the 4th primary cancer-associated mortality globally. As the first identified m6A demethylase for removing RNA methylation modification, fat mass and obesity-associated protein (FTO) plays instrumental roles in cancer development. Therefore, we study the biological functions and oncogenic mechanisms ofFTO in GC tumorigenesis and progression. In our study, FTO expression is obviously upregulated in GC tissues and cells. The upregulation ofFTO is associated with advanced nerve invasion, tumor size, and LNM, as well as the poor prognosis in GC patients, and promoted GC cell viability, colony formation, migration and invasion. Mechanistically, FTO targeted specificity protein 1 and Aurora Kinase B, resulting in the phosphorylation of ataxia telangiectasia mutated and P38and dephosphorylationofP53 . In conclusion, them6AdemethylaseFTO promotes GC tumorigenesis and progression by regulating the SP1-AURKB-ATM pathway, which may highlight the potential ofFTOasa diagnostic biomarker for GC patients’ therapy response and prognosis. |  |\n| Worldwide gastric cancer (GC)poses a critical public health challenge in that it has more than a million new cases and 769,000 deaths worldwide in 20201. Despite the development in diagnosis and treatment, the outcome of advanced GC remains poor, and patients with distant metastases have a less than 5% five-year survival rate2–4. Therefore, identifying novel therapeutic targets and understanding the molecular mechanisms underlying GC development are critical to improving the early diagnosis of GC.\u003Cbr>Recently, the function of RNA modifications in cancers has garnered growing research attention5. The most prevalent form of methylation in RNAs is N6-methyladenosine (m6A), and its dysregulation has been associated with cancer pathogenesis including GC4,6–9. For example, demethylase ALKBH5 inhibits the spread of gastric cancer through moderating PKMYT1 m6A10. By controlling the miR-30c-2-3p/AKT1S1 axis, METTL14-mediated m6A alteration of circORC5 prevents the advancement ofgastric cancer11. Fat mass and obesity-associatedprotein(FTO)is the first identified m6A demethylase to specifically remove RNA m6A modification12. FTO is overexpressed in many cancers and has obvious impacts on the development of cancers13, 14, by regulating mRNA splicing, stability, and translation9, 15. However, the underlying mechanisms ofFTO in GC tumorigenesis remain a mystery. | Specificity protein 1 (SP1) is a transcription factor that enhances transcription of oncogenes during cell proliferation, differentiation, and apoptosis16,17. For example, USP39 promotes the tumorigenesis of hepatocellular carcinoma by stabilizing and deubiquitinating SP118. LncRNA THAP7-AS1 promotes oncogenesis by enabling CUL4B entrance into the nucleus. It is transcriptionally triggered by SP1 and post-transcriptionally maintained by METTL3-mediated m6A modification19. The Mitotic syndicateAurora Kinase B (AURKB) is a key regulator of mitosis and cisplatin resistance, promoting GC growth, development, and metastasis16, 17,20. Germ-line mutations in the ataxia telangiectasia mutated (ATM) gene lead to ataxia-telangiectasia syndrome, manifested by increased susceptibility to malignancies21,22.\u003Cbr>The purpose of this study was to examine the function ofFTO in GC proliferation and metastasis. We identified a novel signaling pathway involving SP1, AURKB and ATM that is necessary for GC progression, providing potential biomarkers for developing therapeutic strategies against GC.\u003Cbr>Resu","cbCaik2kUvnVK5v8","https://ap.wps.com/l/cbCaik2kUvnVK5v8","pdf",3662357,13,"English","# Introduction\n## Background on gastric cancer and RNA m6A modifications\n## FTO and its potential mechanisms in GC\n# Results\n## Upregulation of FTO in GC and association with prognosis","[{\"question\":\"What is the main biological focus of the study in gastric cancer?\",\"answer\":\"The study focuses on the RNA demethylase FTO and how it contributes to gastric cancer tumorigenesis and progression through downstream signaling mechanisms.\"},{\"question\":\"How does FTO expression relate to clinical outcomes in gastric cancer?\",\"answer\":\"FTO is upregulated in malignant gastric tissues and its higher expression is associated with adverse prognosis, including worse survival measures and correlations with advanced invasion and metastasis parameters.\"},{\"question\":\"What signaling pathway does the study propose for FTO-driven progression?\",\"answer\":\"The study proposes that FTO promotes gastric cancer progression by regulating the SP1-AURKB-ATM pathway, affecting phosphorylation and dephosphorylation of key proteins involved in the process.\"}]","RNA demethylase FTO participates in malignant progression of gastric cancer by regulating SP1-AURKB-ATM pathway | PDF",1789997264,33]