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This study investigates how the demethylase FTO regulates TNBC through an m6A-dependent pathway: FTO modulates miR-17-5p maturation, which then alters ZBTB4 expression via miR-17-5p–linked regulation. Bioinformatic analyses across GEO and TCGA identify FTO as a key factor. Cellular overexpression and xenograft models show that FTO restrains TNBC proliferation, migration, and invasion, supporting the FTO/miR-17-5p/ZBTB4 axis and suggesting new targets for TNBC therapy.",{"@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/demethylase-fto-inhibits-the-occurrence-and-development-of-triple-negative-breast-cancer-by-blocking-m6a-dependent-mir-17-5p-maturation-induced-zbtb4-depletion/340930/",{"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/demethylase-fto-inhibits-the-occurrence-and-development-of-triple-negative-breast-cancer-by-blocking-m6a-dependent-mir-17-5p-maturation-induced-zbtb4-depletion/340930.png","ImageObject",300,407,{"name":92,"@type":93},"Patrick","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the proposed role of FTO in triple-negative breast cancer (TNBC)?","Question",{"text":112,"@type":113},"FTO is proposed to regulate TNBC by modulating m6A-dependent maturation of miR-17-5p, which subsequently affects ZBTB4 expression and TNBC progression.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does FTO influence miR-17-5p according to the study?",{"text":117,"@type":113},"The study reports that FTO can regulate miR-17-5p maturation through an m6A-dependent mechanism, impacting downstream gene expression.",{"name":119,"@type":110,"acceptedAnswer":120},"What experimental evidence supports the FTO/miR-17-5p/ZBTB4 regulatory axis?",{"text":121,"@type":113},"Overexpression studies in TNBC cells show reduced proliferation, migration, and invasion, and xenograft nude mouse experiments plus clinical sample analysis further confirm the regulatory axis.","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},340930,1790715724,{"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":39,"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},549758146520,"https://ap-avatar.wpscdn.com/avatar/80002397d8c0411e94?_k=1775819394049821470","Original Article  \nDemethylase FTO inhibits the occurrence and development of triple-negative breast cancer by blocking m6A-dependent miR-17-5p maturation-induced ZBTB4 depletion  \nJingyi Ni1, Xiaoyun Lu2, Xiangxiang Gao1, Conghui Jin 1, and Junfeng Mao3, *  \n1 Department of Oncology, Affiliated Tumor Hospital of Nantong University, Nantong 226361, China, 2Department of Pathology, Affiliated Tumor Hospital of Nantong University, Nantong 226361, China, and 3Department of Breast Surgery, Affiliated Tumor Hospital of Nantong University, Nantong 226361, China  \n*Correspondence address. Tel: +86-13773650328; E-mail: [5300346@ntu.edu.cn](5300346@ntu.edu.cn)[ ](5300346@ntu.edu.cn)Received 28 June 2023 Accepted 25 August 2023  \nAbstract  \nTriple-negative breast cancer (TNBC) is a subtype of breast cancer, and its mechanisms of occurrence and development remain unclear. In this study, we aim to investigate the role and molecular mechanisms ofthe demethylase FTO (fat mass and obesity-associated protein) in TNBC. Through analysis of public databases, we identify that FTO may regulate the maturation of miR-17-5p and subsequently influence the expression of zinc finger and BTBdomain-containing protein 4 (ZBTB4), thereby affecting the occurrence and progression of TNBC. We screen for relevant miRNAs and mRNAs from the GEO and TCGA databases and find that the FTO gene may play a crucial role in TNBC. In vitro cell experiments demonstrate that overexpression of FTO can suppress the proliferation, migration, and invasion ability of TNBC cells and can regulate the maturation of miR-17-5p through an m6A-dependent mechanism. Furthermore, we establish a xenograft nude mouse model and collect clinical samples to further confirm the role and impact of the FTO/ miR-17-5p/ZBTB4 regulatory axis in TNBC. Our findings unveil the potential role of FTO and its underlying molecular mechanisms in TNBC, providing new perspectives and strategies for the research and treatment of TNBC.  \nKey words FTO demethylase, m6A modification, miR-17-5p, ZBTB4, triple-negative breast cancer  \nIntroduction  \nTriple-negative breast cancer (TNBC) is a clinically distinct subtype of breast cancer characterized by the lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) [1] . Compared to other types of breast cancer, TNBC cases have a higher risk of recurrence and a shorter disease-free survival period [2] . The treatment of TNBC has certain challenges mainly because it is insensitive to conventional hormone therapy and HER2-targeted therapy and currently relies mainly on chemotherapy [3] . Although chemotherapy has significant effects in the initial treatment of TNBC, drug resistance can develop in many cases over time [4–6] . Therefore, exploring new treatment strategies and understanding the molecular mechanisms leading to the occurrence and development ofTNBC have important clinical significance [3] .  \nThe demethylase FTO, an RNA modification enzyme with  \ndemethylation activity, has been proven to play an important role in various physiological and pathological processes in recent years, especially in tumor biology [7–11] . FTO mainly regulates RNA stability and translation efficiency by catalyzing the N6-methyladenosine (m6A) modification, thereby affecting cellular physiological activities [12] . m6A modification has been proven to play a crucial role in the occurrence and development of tumors, and FTO, as the“eraser” of m6A, may also affect tumor biology by altering the m6A modification status of RNA [13], but its specific mechanism is still unclear.  \nm6A modification is considered the most abundant endogenous mRNA modification and profoundly impacts a series of biological processes, such as mRNA stability and translation [14] . m6A modification could be added by “writers”, removed by “erasers”, and recognized by “readers”, forming a complete regulatory network, thereby affecting the fate of RNA","cbCaiuovFL4Fa7gg","https://ap.wps.com/l/cbCaiuovFL4Fa7gg","pdf",3030336,15,"English","# Abstract\n# Introduction\n# Materials and Methods","[{\"question\":\"What is the proposed role of FTO in triple-negative breast cancer (TNBC)?\",\"answer\":\"FTO is proposed to regulate TNBC by modulating m6A-dependent maturation of miR-17-5p, which subsequently affects ZBTB4 expression and TNBC progression.\"},{\"question\":\"How does FTO influence miR-17-5p according to the study?\",\"answer\":\"The study reports that FTO can regulate miR-17-5p maturation through an m6A-dependent mechanism, impacting downstream gene expression.\"},{\"question\":\"What experimental evidence supports the FTO/miR-17-5p/ZBTB4 regulatory axis?\",\"answer\":\"Overexpression studies in TNBC cells show reduced proliferation, migration, and invasion, and xenograft nude mouse experiments plus clinical sample analysis further confirm the regulatory axis.\"}]","Demethylase FTO inhibits the occurrence and development of triple-negative breast cancer by blocking m6A-dependent miR-17-5p maturation-induced ZBTB4 depletion | PDF",1790039585,38]