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Chemical modification improves nuclease resistance and stability, yet delivery remains a barrier, prompting vehicle-free nanoparticle and membrane-crossing strategies, informed by siRNA experience such as Patisiran. This review traces evolving microRNA mimic approaches.",{"@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/the-promise-and-pursuit-of-micrornas-for-cancer-treatment/352103/",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/the-promise-and-pursuit-of-micrornas-for-cancer-treatment/352103.png","ImageObject",300,407,{"name":42,"@type":43},"dhado","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-02","2026-09-22",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"How do microRNAs contribute to cancer biology?","Question",{"text":63,"@type":64},"MicroRNAs regulate post-transcriptional gene expression and can be under expressed as tumor suppressor microRNAs or over expressed as oncogenic microRNAs. They influence processes such as metastasis, apoptosis, and proliferation through effects on target mRNAs.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What makes microRNA mimic therapy challenging?",{"text":68,"@type":64},"Without chemical modification, microRNAs are too vulnerable to achieve lasting therapeutic value. Even with stability improvements, delivery is limited because microRNA mimics do not cross cell membranes without a vehicle.",{"name":70,"@type":61,"acceptedAnswer":71},"How are microRNA mimics engineered to improve stability and cellular delivery?",{"text":72,"@type":64},"Chemical modifications provide nuclease resistance and greater stability. Additional strategies enable membrane crossing, including substituting uracil with 5-fluorouracil, while nanoparticle approaches can address delivery but may also trigger inflammatory reactions.","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},352103,1790655440,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,119,122,126],{"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":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},"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":145},5909893218464,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","Review  \nThe Promise and Pursuit of MicroRNAs for Cancer Treatment  \nCamaleta Boothe 1,2, Arianna Rossi 1,2, Jenniffer Kalil 1,2 and Jean J. Latimer 1,2, *  \nAcademic Editor: Dirk Geerts  \nReceived: 18 June 2026  \nRevised: 18 July 2026  \nAccepted: 21 July 2026  \nPublished: 24 July 2026  \nCopyright: © 2026 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.  \n1 Pharmaceutical Sciences, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; [ar4734@mynsu.nova.edu](ar4734@mynsu.nova.edu) (A.R.); [jkalil@nova.edu](jkalil@nova.edu) (J.K.)  \n2 NSU AutoNation Institute for Breast Cancer Research and Care, Nova Southeastern University, Fort Lauderdale, FL 33328, USA  \n* [Correspondence: jl1543@nova.edu](Correspondence: jl1543@nova.edu)  \nAbstract  \nIn spite of at least six discrete classes of drugs available for cancer treatment, the quest for more biologic drugs continues. One type of biologic molecule that occurs naturally in the body is microRNA. MicroRNAs regulate post-transcriptional gene expression and can be under expressed in cancer (tumor suppressor microRNAs) or over expressed (oncogenic microRNAs) . Strand-specific mimics of microRNAs have been developed and used successfully in vitro, in vivo, and in clinical trials, to control multiple aspects of cancer including metastasis, apoptosis and proliferation. Each microRNA is capable of binding a specific target mRNA or mRNAs, sometimes simultaneously interfering with multiple genes ina single pathway, or binding with a single nodal mRNA. Some microRNAs can facilitate chemotherapy that has stopped working, addressing the issue of drug resistance. Without chemical modification, microRNAs are too vulnerable to have lasting therapeutic value. Chemical modifications to microRNAs have provided nuclease resistance and greater stability and are the basis for microRNA mimics that can be used therapeutically. However, without a vehicle, microRNA mimics do not cross cell membranes. These nanoparticles can cause inflammatory reactions in patients. Additional modifications that enabled microRNA mimics to cross cell membranes include substituting uracil with 5-fluorouracil. Lessons from an siRNA therapeutic called Patisiran offer a roadmap for future success for microRNAs in cancer. This review provides a historical perspective of the continuing evolution of microRNA mimics for cancer treatment.  \nKeywords: microRNA; cancer therapeutics; microRNA mimics; antagomirs; oncomiRs; tumor suppressor microRNAs; RNA therapeutics; gene regulation; 5-FU-modified microRNA; RNAi  \n1. Introduction  \nCancer continues to be the second most burdensome disease globally with approximately 20 million new cases and 9.7 million deaths annually [1] . Despite advances in cancer screening, diagnosis and treatment, including radiation, chemotherapy, endocrine therapy, immune and targeted therapies, treatment resistance remains the greatest clinical challenge. Consequently the search for more effective, less toxic treatment options continues.  \nRNAs can regulate gene expression in plants and mammals. It was not until the discovery of the microRNA let-7 that the fundamental importance of microRNA across most genomes including humans was recognized [2] . While these findings were considered unusual, scientists in the early 2000s found many similar small RNAs in both plants and other animals. The important functional role that microRNAs play has since been revealed  \nto be their role in regulation of gene expression with subsequent applications in many diseases as well as use in drug therapy, disease diagnosis and prognosis [3] .  \nIn humans, microRNAs are transcribed from DNA into RNA molecules through a series of processes (Figure 1) . Two essential enzymes, Drosha and Dicer, are responsible for the cleaving of these larger RNAs into smaller pieces, namely, primary, pre-and matur","cbCaifIrQHPK2mf2","https://ap.wps.com/l/cbCaifIrQHPK2mf2","pdf",804559,17,"English","# Abstract\n# Introduction\n## Cancer burden and treatment resistance\n## Discovery and biological role of microRNAs\n## Biogenesis and gene regulation mechanisms\n## MicroRNA targeting and silencing pathways","[{\"question\":\"How do microRNAs contribute to cancer biology?\",\"answer\":\"MicroRNAs regulate post-transcriptional gene expression and can be under expressed as tumor suppressor microRNAs or over expressed as oncogenic microRNAs. They influence processes such as metastasis, apoptosis, and proliferation through effects on target mRNAs.\"},{\"question\":\"What makes microRNA mimic therapy challenging?\",\"answer\":\"Without chemical modification, microRNAs are too vulnerable to achieve lasting therapeutic value. Even with stability improvements, delivery is limited because microRNA mimics do not cross cell membranes without a vehicle.\"},{\"question\":\"How are microRNA mimics engineered to improve stability and cellular delivery?\",\"answer\":\"Chemical modifications provide nuclease resistance and greater stability. Additional strategies enable membrane crossing, including substituting uracil with 5-fluorouracil, while nanoparticle approaches can address delivery but may also trigger inflammatory reactions.\"}]","The Promise and Pursuit of MicroRNAs for Cancer Treatment | PDF",1790097709,43]