[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-333898-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-333898-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":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","klf1-activates-rac3-to-mediate-fatty-acid-synthesis-and-enhance-cisplatin-resistance-in-bladder-cancer-cells","KLF1 Activates RAC3 to Mediate Fatty Acid Synthesis and Enhance Cisplatin Resistance in Bladder Cancer Cells","","Cisplatin is a frontline therapy for bladder cancer, yet acquired resistance reduces clinical effectiveness. RAC3 is linked to chemoresistance, but its function in cisplatin resistance in bladder cancer cells remained unclear. Bioinformatics and qPCR assessed RAC3 in bladder cancer, while GSEA mapped RAC3-enriched pathways tied to fatty acid synthesis via FASN. Dual-luciferase, ChIP, and cell-line assays using T24/DDP evaluated KLF1–RAC3 regulation, proliferation, IC50 shifts, and changes in fatty acid synthesis, including RAC3 knockdown and KLF1 modulation. The KLF1/RAC3 axis promotes cisplatin resistance and may be a therapeutic target.",{"@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/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/klf1-activates-rac3-to-mediate-fatty-acid-synthesis-and-enhance-cisplatin-resistance-in-bladder-cancer-cells/333898/",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/klf1-activates-rac3-to-mediate-fatty-acid-synthesis-and-enhance-cisplatin-resistance-in-bladder-cancer-cells/333898.png","ImageObject",300,407,{"name":42,"@type":43},"Riley","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",5,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What problem does the study address in bladder cancer treatment?","Question",{"text":63,"@type":64},"The study targets cisplatin resistance in bladder cancer, which limits cisplatin’s effectiveness after resistance develops.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How is RAC3 connected to fatty acid synthesis and cisplatin resistance?",{"text":68,"@type":64},"RAC3 is enriched in fatty-acid-synthesis-related pathways, correlates with FASN, and functionally contributes to cisplatin resistance in cisplatin-resistant bladder cancer cells.",{"name":70,"@type":61,"acceptedAnswer":71},"What upstream regulator is identified and what is its role?",{"text":72,"@type":64},"Kruppel-like factor 1 (KLF1) emerges as a key upstream regulator that activates RAC3, promotes fatty acid synthesis, and enhances cisplatin resistance.","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},333898,1790161728,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,100,105,110,114,119,122,126],{"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":55,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},"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":55,"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":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":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":112,"preview_page_count":4},1374391975076,"https://ap-avatar.wpscdn.com/avatar/14000253ca4ec9f6853?x-image-process=image/resize,m_fixed,w_180,h_180&k=1783305029341752051","KLF1 Activates RAC3 to Mediate Fatty Acid Synthesis and Enhance Cisplatin Resistance in Bladder Cancer Cells  \nAmerican Journal of Men’s Health September-October 1–12  \n􀀂 The Author(s) 2024  \nArticle reuse guidelines: [sagepub.com/journals-permissions](sagepub.com/journals-permissions)[ ](sagepub.com/journals-permissions)[DOI: 10.1177/15579883241273305](DOI: 10.1177/15579883241273305)[ ](DOI: 10.1177/15579883241273305)[journals.sagepub.com/home/jmh](journals.sagepub.com/home/jmh)  \nLide Song 1, Qi Xu 1, Rong Chen 1, Wanghong Sun 1, and Jianfei Zhan 1  \nAbstract  \nWhile cisplatin remains a frontline treatment for bladder cancer (BCa), the onset of resistance greatly hampers its effectiveness. RAC3 is closely linked to chemoresistance in cancer cells, but its specific role in cisplatin resistance within BCais still elusive. RAC3 expression in BCa was analyzed using bioinformatics and quantitative polymerase chain reaction (qPCR). The gene set enrichment analysis (GSEA) identified RAC3-enriched pathways and the correlation between RAC3 and fatty acid synthase (FASN), a gene involved in fatty acid synthesis. Potential upstream transcription factors of RAC3 were predicted and their interaction with RAC3 was confirmed via dual-luciferase and chromatin immunoprecipitation (ChIP) assays. T24/DDP, a cisplatin-resistant BCa cell line, was established to probe into the regulatory role of RAC3 in cisplatin resistance. Cell proliferation was evaluated by colony formation and the IC50 values after cisplatin treatment were determined using cell counting kit-8 (CCK-8). The levels of free fatty acids and triglycerides (TGs), as well as the expression of DGAT2 and FASN proteins, were measured to gauge the extent of fatty acid synthesis in cells. Elevated expression of RAC3 was observed in BCa and the cisplatin-resistant BCa cells (T24/DDP). The knockdown of RAC3 within T24/DDP cells was demonstrated to counteract cisplatin resistance. Subsequent analyses identified RAC3 as being notably enriched in the fatty acid synthesis pathway, with Kruppel-like factor 1 (KLF1) emerging as a key upstream regulator. The overexpression of RAC3 was correlated with increased cisplatin resistance in T24/DDP cells, an effect that was mitigated by the addition of the FASN inhibitor, Orlistat. Furthermore, the downregulation of KLF1 suppressed RAC3 expression, disrupted fatty acid synthesis, and attenuated cisplatin resistance in T24/DDP cells. Conversely, the co-overexpression of RAC3 counteracted the effects conferred by KLF1 knockdown. Our study has validated that KLF1 activates RAC3 to mediate fatty acid synthesis and promote cisplatin resistance in BCa, suggesting the KLF1/RAC3 axis as a potential target for combating cisplatin-resistant BCa.  \nKeywords  \nbladder cancer, cisplatin resistance, fatty acid synthesis, KLF1, RAC3  \nReceived June 26, 2024; revised September 10, 2024; accepted July 5, 2024  \nIntroduction  \nBladder cancer (BCa) is a prevalent malignant neoplasm of the urinary system, severely jeopardizing human health and survival (Lenis et al., 2020) . Cisplatin-based chemotherapy is a preferred choice for BCa patients, which is effective in controlling tumor progression and reducing recurrence rates (Stone, 2023) . Nonetheless, the onset of acquired cisplatin resistance often threatens the success of treatments (Choi et al., 2014; Kamat et al., 2016) .  \nUncovering the molecular mechanisms of resistance in BCa cells is sure to go a long way toward optimized therapeutic strategies.  \n1 Department of Urology, Zhuji People’s Hospital, Zhuji, China  \nCorresponding Author:  \nJianfei Zhan, Department of Urology, Zhuji People’s Hospital, No. 9 Jianmin Road, Taozhu Street, Zhuji, 311800, China.  \nEmail: z_[jf1353@163.com](jf1353@163.com)  \n Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons  \nAttribution-NonCommercial 4.0 License ([https://creativecommons.org/licenses/by-nc/4.0/](https://creativecom","cbCaiirlplfUxjd9","https://ap.wps.com/l/cbCaiirlplfUxjd9","pdf",2758451,12,"English","# Abstract\n# Introduction","[{\"question\":\"What problem does the study address in bladder cancer treatment?\",\"answer\":\"The study targets cisplatin resistance in bladder cancer, which limits cisplatin’s effectiveness after resistance develops.\"},{\"question\":\"How is RAC3 connected to fatty acid synthesis and cisplatin resistance?\",\"answer\":\"RAC3 is enriched in fatty-acid-synthesis-related pathways, correlates with FASN, and functionally contributes to cisplatin resistance in cisplatin-resistant bladder cancer cells.\"},{\"question\":\"What upstream regulator is identified and what is its role?\",\"answer\":\"Kruppel-like factor 1 (KLF1) emerges as a key upstream regulator that activates RAC3, promotes fatty acid synthesis, and enhances cisplatin resistance.\"}]","KLF1 Activates RAC3 to Mediate Fatty Acid Synthesis and Enhance Cisplatin Resistance in Bladder Cancer Cells | PDF",1790004516]