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This review analyzes how microRNAs and circular RNAs contribute to breast cancer biology and supports their use as non-invasive biomarkers. In silico tools and public datasets are used to propose mRNA/circRNA/miRNA axes linked to early tumor initiation, then tested with Kaplan–Meier survival analysis and miRNA enrichment using patient data. Joint circRNA–miRNA differential expression in body fluids or exosomes increases confidence.",{"@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/circrnas-and-mirnas-key-player-duo-in-breast-cancer-dynamics-and-biomarkers-for-breast-cancer-early-detection-and-prevention/331628/",{"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/circrnas-and-mirnas-key-player-duo-in-breast-cancer-dynamics-and-biomarkers-for-breast-cancer-early-detection-and-prevention/331628.png","ImageObject",300,407,{"name":92,"@type":93},"Genevieve","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main purpose of this review?","Question",{"text":112,"@type":113},"To summarize the roles of miRNAs and circRNAs in breast cancer dynamics and evaluate them as non-invasive biomarker candidates for early detection and prevention.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How are mRNA/circRNA/miRNA axes identified and validated?",{"text":117,"@type":113},"The review uses in silico tools and two GEO datasets to identify candidate axes, then validates them with Kaplan–Meier survival plots and enrichment analysis based on patient miRNA expression.",{"name":119,"@type":110,"acceptedAnswer":120},"Why does combined analysis of circRNAs and miRNAs improve biomarker confidence?",{"text":121,"@type":113},"Evaluating coupled differential expression in body fluids or exosomes provides greater confidence than analyzing either circRNAs or miRNAs alone, with more axes offering even stronger support.","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},331628,1790146296,{"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":24,"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},1374391974585,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Review  \nCircRNAs and miRNAs: Key Player Duo in Breast Cancer Dynamics and Biomarkers for Breast Cancer Early Detection and Prevention  \nNour Maatouk 1, Abdallah Kurdi 2, Sarah Marei 1, Rihab Nasr 3 and Rabih Talhouk 1, *  \nCitation: Maatouk, N.; Kurdi, A.; Marei, S.; Nasr, R.; Talhouk, R. CircRNAs and miRNAs: Key Player Duo in Breast Cancer Dynamics and Biomarkers for Breast Cancer Early Detection and Prevention. Int. J. Mol. Sci. 2024, 25, 13056. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms252313056](10.3390/ijms252313056)  \nAcademic Editor: Bertrand Kaeffer  \nReceived: 25 October 2024  \nRevised: 15 November 2024  \nAccepted: 19 November 2024  \nPublished: 4 December 2024  \nCopyright: © 2024 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 Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut 11-0236, Lebanon; [nam43@mail.aub.edu](nam43@mail.aub.edu) (N.M.); [shm32@mail.aub.edu](shm32@mail.aub.edu) (S.M.)  \n2 Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut 11-0236, Lebanon; [ak161@aub.edu.lb](ak161@aub.edu.lb)  \n3 Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 11-0236, Lebanon; [rn03@aub.edu.lb](rn03@aub.edu.lb)  \n* Correspondence: [rtalhouk@aub.edu.lb](rtalhouk@aub.edu.lb)  \nAbstract: Breast cancer (BC) remains a significant global health issue, necessitating advanced molecular approaches for early detection and prevention. This review delves into the roles of microRNAs (miRNAs) and circular RNAs (circRNAs) in BC, highlighting their potential as non-invasive biomarkers. Utilizing in silico tools and databases, we propose a novel methodology to establish mRNA/circRNA/miRNA axes possibly indicative of early detection and possible prevention. We propose that during early tumor initiation, some changes in oncogene or tumor suppressor gene expression (mRNA) are mirrored by alterations in corresponding circRNAs and reciprocal changes in sponged miRNAs affecting tumorigenesis pathways. We used two Gene Expression Omnibus (GEO) datasets and identified five mRNA/circRNA/miRNA axes as early possible tumor initiation biomarkers. We further validated the proposed axes through a Kaplan–Meier (KM) plot and enrichment analysis of miRNA expression using patient data. Evaluating coupled differential expression of circRNAs and miRNAs in body fluids or exosomes provides greater confidence than assessing either, with more axes providing even greater confidence. The proposed methodology not only improves early BC detection reliability but also has applications for other cancers, enhancing preventive measures.  \nKeywords: breast cancer; epigenetics; non-coding RNAs  \n1. Introduction  \nCancer is a dynamic, highly heterogeneous disease [1] . Despite the dramatic improvement in cancer research, our understanding of the tumor initiation mechanisms lags far behind. The conversion from a nonmalignant to a malignant cell is now better understood due to advances in molecular diagnostics and sequencing technologies [2] . Commonly, a tumor arises through the acquisition of mutations in susceptible cell types [3] . The progression of the disease occurs specifically through the accumulation of sequential alterations which, combined, enhance genome instability that contributes to the acquisition of cancer hallmarks [4] . While genetic mutations are the primary drivers of tumor initiation and progression, a growing body of evidence implicates the fundamental role of epigenetic regulation [5] .  \nBreast cancer (BC) is the second leading cause of cancer-related death among wom","cbCaisjQWihD3s3j","https://ap.wps.com/l/cbCaisjQWihD3s3j","pdf",1114869,25,"English","# Abstract\n# Introduction\n## Breast cancer burden and classification\n## Epigenetic regulation and tumor initiation\n## Molecular subtypes and diagnostic advances\n# Review focus: miRNAs and circRNAs in breast cancer\n## Dysregulated expression and oncogenesis\n## Proposed biomarker axes and validation","[{\"question\":\"What is the main purpose of this review?\",\"answer\":\"To summarize the roles of miRNAs and circRNAs in breast cancer dynamics and evaluate them as non-invasive biomarker candidates for early detection and prevention.\"},{\"question\":\"How are mRNA/circRNA/miRNA axes identified and validated?\",\"answer\":\"The review uses in silico tools and two GEO datasets to identify candidate axes, then validates them with Kaplan–Meier survival plots and enrichment analysis based on patient miRNA expression.\"},{\"question\":\"Why does combined analysis of circRNAs and miRNAs improve biomarker confidence?\",\"answer\":\"Evaluating coupled differential expression in body fluids or exosomes provides greater confidence than analyzing either circRNAs or miRNAs alone, with more axes offering even stronger support.\"}]","CircRNAs and miRNAs: Key Player Duo in Breast Cancer Dynamics and Biomarkers for Breast Cancer Early Detection and Prevention | PDF",1789994368,63]