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Predicted FBXW9 substrates implicate TP53 as a hub; FBXW9 knockdown increases TP53–p21 signaling, elevates stemness associations, and suppresses breast cancer proliferation and cell-cycle progression.",{"@graph":14,"@context":73},[15,34,56],{"@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/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/a-comprehensive-analysis-revealing-fbxw9-as-a-potential-prognostic-and-immunological-biomarker-in-breast-cancer/380988/",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/a-comprehensive-analysis-revealing-fbxw9-as-a-potential-prognostic-and-immunological-biomarker-in-breast-cancer/380988.png","ImageObject",300,407,{"name":42,"@type":43},"Finn","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-25","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",8,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What method was used to study FBXWs and FBXW9?","Question",{"text":63,"@type":64},"Integrative bioinformatic analysis was performed on transcriptome profiles from TCGA datasets, followed by cell-based assays to validate FBXW9 functions in breast cancer cells.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How is FBXW9 related to prognosis and immunology in cancer?",{"text":68,"@type":64},"FBXW9 expression correlates with patient prognosis across cancer types, is linked to immune-cell infiltration, and is associated with poor outcomes in patients receiving anti-PD1 therapy.",{"name":70,"@type":61,"acceptedAnswer":71},"What biological pathway is suggested by the study for FBXW9?",{"text":72,"@type":64},"Predicted substrates highlight TP53 as a hub gene; downregulation of FBXW9 increases p21 expression in breast cancer cells, consistent with TP53-related regulation.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},380988,1791289814,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},"Research & Report",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":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"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":55,"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":108},34359740700684,"https://ap-avatar.wpscdn.com/avatar/1f400023980c374ae676?_k=1777273430885731487","Article  \nA Comprehensive Analysis Revealing FBXW9 as a Potential Prognostic and Immunological Biomarker in Breast Cancer  \nShiyi Yu 1,2, Zhengyan Liang 1,2, Zhehao Fan 1,2, Binjie Cao 1,2, Ning Wang 1,2, Rui Wu 1,2 and Haibo Sun 1,2, *  \nCitation: Yu, S.; Liang, Z.; Fan, Z.; Cao, B.; Wang, N.; Wu, R.; Sun, H. A Comprehensive Analysis Revealing FBXW9 as a Potential Prognostic and Immunological Biomarker in Breast Cancer. Int. J. Mol. Sci. 2023, 24, 5262 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms24065262  \nAcademic Editor: Diana Gherman  \nReceived: 17 January 2023  \nRevised: 22 February 2023  \nAccepted: 28 February 2023  \nPublished: 9 March 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, China; [007585@yzu.edu.cn](007585@yzu.edu.cn) (S.Y.); [18202730560@163.com](18202730560@163.com) (Z.L.); [fzhehao@126.com](fzhehao@126.com) (Z.F.); [yzucbj@163.com](yzucbj@163.com) (B.C.); [wn18435166884@163.com](wn18435166884@163.com) (N.W.); [wr15004421751@163.com](wr15004421751@163.com) (R.W.)  \n2 Jiangsu Key Laboratory of Experimental & Translational Non-Coding RNA Research Yangzhou, Yangzhou 225001, China  \n* Correspondence: [frenksun@126.com](frenksun@126.com)  \nAbstract: The WD40 repeat-containing F-box proteins (FBXWs) family belongs to three major classes of F-box proteins. Consistent with the function of other F-box proteins, FBXWs are E3 ubiquitin ligases to mediate protease-dependent protein degradation. However, the roles of several FBXWs remain elusive. In the present study, via integrative analysis of transcriptome profiles from The Cancer Genome Atlas (TCGA) datasets, we found that FBXW9 was upregulated in the majority of cancer types, including breast cancer. FBXW expression was correlated with the prognosis of patients with various types of cancers, especially for FBXW4, 5, 9, and 10 . Moreover, FBXWs were associated with infiltration of immune cells, and expression of FBXW9 was associated with poor prognosis of patients receiving anti-PD1 therapy. We predicted several substrates of FBXW9, and TP53 was the hub gene in the list. Downregulation of FBXW9 increased the expression of p21, a target of TP53, in breast cancer cells. FBXW9 was also strongly correlated with cancer cell stemness, and genes correlated with FBXW9 were associated with several MYC activities according to gene enrichment analysis in breast cancer. Cell-based assays showed that silencing of FBXW9 inhibited cell proliferation and cell cycle progression in breast cancer cells. Our study highlights the potential role of FBXW9 as a biomarker and promising target for patients with breast cancer.  \nKeywords: FBXWs; FBXW9; ubiquitin; immunology; pan-cancer  \n1. Introduction  \nAlthough advances have been achieved in understanding their mechanisms, cancers remain a major threat to humans and a serious public health problem worldwide [1]. Owing to the public easily accessed database, pan-cancer analysis has been performed on many proteins and non-coding RNAs [2,3], which could provide valuable information for cancer studies given that hallmarks are shared in cancers of various origins [4] .  \nUbiquitination is a crucial biological process for protein turnover [5,6] . This process is achieved via the cooperation of the E1 enzyme, E2 enzyme, and E3 ligase [7,8] . F-box proteins are the most well-characterized E3 ligases among hundreds [9] . Generally, F-box proteins specifically bind to phosphorylated substrates, leading to proteolytic ubiquitination (Lysine 48, Lysine 11) or non-proteolytic ubiquitination (Lysine 63) [10] . ","cbCaija7GFTZnDLi","https://ap.wps.com/l/cbCaija7GFTZnDLi","pdf",13293839,16,"English","# Abstract\n# Introduction\n## Background on cancers and pan-cancer analysis\n## Ubiquitination and F-box proteins\n# Results\n## Analysis of mRNA levels across tumor and normal tissues","[{\"question\":\"What method was used to study FBXWs and FBXW9?\",\"answer\":\"Integrative bioinformatic analysis was performed on transcriptome profiles from TCGA datasets, followed by cell-based assays to validate FBXW9 functions in breast cancer cells.\"},{\"question\":\"How is FBXW9 related to prognosis and immunology in cancer?\",\"answer\":\"FBXW9 expression correlates with patient prognosis across cancer types, is linked to immune-cell infiltration, and is associated with poor outcomes in patients receiving anti-PD1 therapy.\"},{\"question\":\"What biological pathway is suggested by the study for FBXW9?\",\"answer\":\"Predicted substrates highlight TP53 as a hub gene; downregulation of FBXW9 increases p21 expression in breast cancer cells, consistent with TP53-related regulation.\"}]","A Comprehensive Analysis Revealing FBXW9 as a Potential Prognostic and Immunological Biomarker in Breast Cancer | PDF",1790243056]