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Mounting evidence supports ferroptosis roles in tumorigenesis and cancer therapy, yet many mechanisms of tumor ferroptosis remain incomplete. Non-coding RNAs form regulatory networks controlling ferroptosis genes, while mediating communication among cancer, stromal, and immune cells in the tumor microenvironment. These ferroptosis-related RNAs are promising immunotherapy targets and may help overcome drug resistance, and nanomedicine delivery of ncRNAs is crucial. This review consolidates regulatory mechanisms across cancers, details functions in the tumor microenvironment, evaluates clinical potential, and highlights unresolved questions.",{"@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/non-coding-rnas-as-master-regulators-of-ferroptosis-in-cancer-mechanisms-and-clinical-implications/349395/",{"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/non-coding-rnas-as-master-regulators-of-ferroptosis-in-cancer-mechanisms-and-clinical-implications/349395.png","ImageObject",300,407,{"name":92,"@type":93},"Kurz","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What defines ferroptosis as a type of regulated cell death?","Question",{"text":112,"@type":113},"Ferroptosis is characterized by intracellular iron accumulation and increased cytotoxic lipid peroxides, with regulation involving redox homeostasis, iron metabolism, lipid metabolism, and signaling cascades.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do non-coding RNAs influence ferroptosis in cancer?",{"text":117,"@type":113},"Non-coding RNAs, including microRNAs, long noncoding RNAs, and circular RNAs, form regulatory networks that directly regulate ferroptosis-related genes or enzymes and indirectly modulate factors associated with ferroptosis.",{"name":119,"@type":110,"acceptedAnswer":120},"Why are ferroptosis-related RNAs considered promising for cancer treatment?",{"text":121,"@type":113},"Because they can act as mediators in the tumor microenvironment and emerge as targets for immunotherapy and for overcoming drug resistance. 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Molecular Cancer (2026) 25:157 Molecular Cancer  \n[https://doi.org/10.1186/s12943-026-02666-x](https://doi.org/10.1186/s12943-026-02666-x)  \nREVIEW Open Access  \nNon-coding RNAs as master regulators  offerroptosis in cancer: mechanismsand clinical implications  \nHaoyang Mo1,2†, Yao Xie3†, Hao Zhang4,5†, Yunyi Liu3, Wantao Wu6, Zhiwei Xia7*, Peng Luo8*, Zhixiong Liu 1,2,9,10* and Quan Cheng1,2,5,9,11*  \nAbstract  \nFerroptosis is a non-apoptotic form of cell death characterized by intracellular iron accumulation and the subsequent elevation of cytotoxic lipid peroxides. Various cellular metabolic pathways intricately regulate this process, including redox homeostasis, iron metabolism, lipid metabolism, and other signaling cascades. Increasing evidence substantiates the critical role of ferroptosis in tumorigenesis and cancer therapy. However, our current understanding of numerous mechanisms underlying tumor ferroptosis remains limited. Noncoding RNAs (ncRNAs) provide a new perspective. Several ncRNAs, particularly microRNAs, long noncoding RNAs, and circular RNAs, are being demonstrated to form a comprehensive regulatory network that exerts direct regulation over ferroptosisrelated genes or enzymes while indirectly modulating regulatory factors associated with ferroptosis. Strikingly, ncRNAs also serve as crucial mediators orchestrating communication between cancer cells, stromal cells, and immune cells within the tumor microenvironment (TME) . Given their substantial potential in tumors and the TME, ferroptosis-related RNAs emerge as promising targets for immunotherapy and overcoming drug resistance. The development of novel nanomedicines for delivering ncRNAs is crucial in advancing antitumor therapy. This review comprehensively elucidates the regulatory mechanisms of ferroptosis-associated ncRNAs across various cancers, sheds light on their functions within the TME, explores their clinical potential to overcome drug resistance, and highlights unresolved questions.  \nKeywords Ferroptosis, Non-coding RNAs, Tumor microenvironment, Immunotherapy, Drug resistance  \n†Haoyang Mo, Yao Xie and Hao Zhang contributed equally to this work.  \n*Correspondence: Zhiwei Xia  \nxiazhiwei201 [1@gmail.com](1@gmail.com)  \nPeng Luo [luopeng@smu.edu.cn](luopeng@smu.edu.cn)[ ](luopeng@smu.edu.cn)Zhixiong Liu [zhixiongliu@csu.edu.cn](zhixiongliu@csu.edu.cn)[ ](zhixiongliu@csu.edu.cn)Quan Cheng [chengquan@csu.edu.cn](chengquan@csu.edu.cn)  \nFull list of author information is available at the end of the article  \nIntroduction  \nIn 2012, Dixon hypothesized that ferroptosis is a nonapoptotic form of controlled, iron-dependent cell death mediated by lipid peroxidation [1]. Ferroptosis is a unique cell death mode that differs morphologically and biochemically from other common regulatory cell death (RCDs) [2]. Ferroptosis cells often exhibit a typical necrotic morphology, characterized by mitochondrial shrinkage, reduction or disappearance of mitochondrial cristae, increased mitochondrial membrane density, and outer membrane rupture, which can be observed under an electron microscope [3–5]. Biochemical features  \n© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulat","cbCaivTLD1l6W6G3","https://ap.wps.com/l/cbCaivTLD1l6W6G3","pdf",3947442,37,"English","# Abstract\n# Introduction\n## Core features and metabolic regulation of ferroptosis\n## Ferroptosis roles in tumors and therapy\n## Immune regulation and signaling pathways","[{\"question\":\"What defines ferroptosis as a type of regulated cell death?\",\"answer\":\"Ferroptosis is characterized by intracellular iron accumulation and increased cytotoxic lipid peroxides, with regulation involving redox homeostasis, iron metabolism, lipid metabolism, and signaling cascades.\"},{\"question\":\"How do non-coding RNAs influence ferroptosis in cancer?\",\"answer\":\"Non-coding RNAs, including microRNAs, long noncoding RNAs, and circular RNAs, form regulatory networks that directly regulate ferroptosis-related genes or enzymes and indirectly modulate factors associated with ferroptosis.\"},{\"question\":\"Why are ferroptosis-related RNAs considered promising for cancer treatment?\",\"answer\":\"Because they can act as mediators in the tumor microenvironment and emerge as targets for immunotherapy and for overcoming drug resistance. The review also emphasizes the importance of developing nanomedicines to deliver ncRNAs.\"}]","Non-coding RNAs as master regulators of ferroptosis in cancer - mechanisms and clinical implications | PDF",1790083126,93]