[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-354169-105":3,"detail-sidebar-cat-0-en-105":80,"doc-detail-354169-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":73,"head_meta":75,"extra_data":77,"updated_unix":79},105,"en","mechanistic-and-preclinical-evaluation-of-sirt3-as-a-therapeutic-target-in-melanoma","Mechanistic and preclinical evaluation of SIRT3 as a therapeutic target in melanoma","","Despite advances in targeted inhibitors and immunotherapies, melanoma remains among the deadliest skin cancers because of high metastatic potential and resistance to existing treatments. Mechanistic targeting is therefore needed. This study investigates SIRT3, a class III histone deacetylase implicated in multiple cellular processes and cancers. Using CRISPR/Cas9 SIRT3 knockout and siRNA, plus patient-derived xenograft and BrafV600E/PtenNULL models, it finds reduced melanoma growth, and shows that combined SIRT1/SIRT3 inhibition with 4′-bromo-resveratrol significantly decreases tumor volume and weight.",{"@graph":14,"@context":72},[15,34,55],{"@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/mechanistic-and-preclinical-evaluation-of-sirt3-as-a-therapeutic-target-in-melanoma/354169/",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/mechanistic-and-preclinical-evaluation-of-sirt3-as-a-therapeutic-target-in-melanoma/354169.png","ImageObject",300,407,{"name":42,"@type":43},"Đào","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":52,"interactionType":53,"userInteractionCount":22},"InteractionCounter",{"@type":54},"ViewAction",{"@type":56,"mainEntity":57},"FAQPage",[58,64,68],{"name":59,"@type":60,"acceptedAnswer":61},"Why does the study focus on SIRT3 in melanoma?","Question",{"text":62,"@type":63},"Melanoma has high metastatic potential and resistance to current therapies. Sirtuins, including SIRT3, have been implicated in many cellular functions and cancers, including melanoma.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"How did the researchers evaluate SIRT3 function in melanoma cells and models?",{"text":67,"@type":63},"They used CRISPR/Cas9-mediated SIRT3 knockout in melanoma cell lines, siRNA against SIRT3, PCR array and NanoString gene-expression profiling, and tested effects in patient-derived xenografts and BrafV600E/PtenNULL mice.",{"name":69,"@type":60,"acceptedAnswer":70},"What is the key therapeutic finding regarding SIRT3 and 4′-bromo-resveratrol?",{"text":71,"@type":63},"While SIRT3 inhibition trends toward reduced tumor growth in vivo, dual SIRT1/SIRT3 inhibition with 4′-bromo-resveratrol significantly decreases tumor volume and weight in melanoma PDX models.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},354169,1790174015,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":88,"show_sort_weight":89,"slug":90},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":92,"show_sort_weight":93,"slug":94},"Exam",70,"exam",{"id":96,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},5,"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":96,"slug":129},19,"General","general",{"code":4,"msg":81,"data":131},{"doc_id":78,"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":22,"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},1374402968488,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Author Manuscr ipt Author Manuscr ipt Author Manuscr ipt Author Manuscript  \n\n| | HHS Public Access\u003Cbr>Author manuscript\u003Cbr>J Derm Oncol. Author manuscript; available in PMC 2026 May 16. |\n| --- | --- |\n\nPublished in final edited form as:  \nJ Derm Oncol. 2026 ; 2(1): . doi:10.1080/29944376.2026.2656032 .  \nMechanistic and preclinical evaluation of SIRT3 as a therapeutic target in melanoma  \nKarla B. Anaya Aldretea, Mary A. Ndiayea, Glorimar Guzmán-Péreza, Gabriella R. Zaemischa, Chandra K. Singha, Gagan Chhabraa, Nihal Ahmada,b  \na Department of Dermatology, University of Wisconsin, Madison, Wisconsin, USA; bWilliam S. Middleton Veterans’ Hospital, Madison, Wisconsin, USA  \nAbstract  \nDespite advances in targeted inhibitors and immunotherapies, melanoma remains one of the deadliest skin cancers due to high metastatic potential and resistance to current therapies. This underscores a critical need for new, mechanism-based treatment strategies. Sirtuins, a family of class III histone deacetylases, have been implicated by our lab and others in numerous cellular functions, diseases, and cancers including melanoma. Here, we sought to extend our findings on the pro-proliferative role of SIRT3 by: (i) defining downstream mechanisms using PCR array and NanoString gene-expression profiling on CRISPR/Cas9-mediated SIRT3 knockout (KO) in melanoma cells; (ii) assessing effects of siRNA against SIRT3 in patient-derived xenograft (PDX) and BrafV600E /PtenNULL melanoma models; and (iii) evaluating efficacy of SIRT3 inhibitor 4′-Bromo-resveratrol (4′-BR) in PDXes. SIRT3 KO significantly reduced growth and colony formation in A375 and G361 melanoma cells. PCR array and NanoString analysis revealed modulation of key cancer-related signaling molecules. In vivo, siRNA-mediated SIRT3 inhibition in melanoma PDXes and BrafV600E /PtenNULL mice trended toward reduced tumor growth. However, dual SIRT1/SIRT3 inhibition with 4′-BR (50 mg/kg, ip, 2x/week) significantly decreased tumor volume and weight in melanoma PDXes. Overall, our data suggests that targeting SIRT1 and SIRT3 together could offer greater therapeutic benefit and should be validated and optimized.  \nThis work was authored as part of the Contributor’s official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 U.S.C. 105, no copyright protection is available for such works under U.S. Law.This is an Open Access article that has been identified as being free of known restrictions under copyright law, including all related and neighboring rights ([https://creativecommons.org/publicdomain/mark/1.0/](https://creativecommons.org/publicdomain/mark/1.0/)). You can copy, modify, distribute and perform the work, even for commercial purposes, all without asking permission. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.  \n✉[CONTACT](CONTACT Nihal Ahmad nahmad@dermatology.wisc.edu 7418 Wisconsin Institutes)[ Nihal Ahmad nahmad@dermatology.wisc.edu 7418 Wisconsin Institutes](CONTACT Nihal Ahmad nahmad@dermatology.wisc.edu 7418 Wisconsin Institutes) for Medical Research, 1111 Highland Ave. Madison, WI 53705.  \nAuthor contributions  \nCRediT: Karla B. Anaya Aldrete: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Visualization, Writing – original draft, Writing – review & editing; Mary A. Ndiaye: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing; Glorimar Guzmán-Pérez: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing – original draft, Writing – review & editing; Gabriella R. Zaemisch: Data curation, Investigation, Validation, Writing – review & editing; Chandra K. Singh: Data curation, ","cbCaimKAmx4WGtJi","https://ap.wps.com/l/cbCaimKAmx4WGtJi","pdf",2369064,21,"English","# Abstract\n# Introduction\n# Author contributions\n# Keywords","[{\"question\":\"Why does the study focus on SIRT3 in melanoma?\",\"answer\":\"Melanoma has high metastatic potential and resistance to current therapies. Sirtuins, including SIRT3, have been implicated in many cellular functions and cancers, including melanoma.\"},{\"question\":\"How did the researchers evaluate SIRT3 function in melanoma cells and models?\",\"answer\":\"They used CRISPR/Cas9-mediated SIRT3 knockout in melanoma cell lines, siRNA against SIRT3, PCR array and NanoString gene-expression profiling, and tested effects in patient-derived xenografts and BrafV600E/PtenNULL mice.\"},{\"question\":\"What is the key therapeutic finding regarding SIRT3 and 4′-bromo-resveratrol?\",\"answer\":\"While SIRT3 inhibition trends toward reduced tumor growth in vivo, dual SIRT1/SIRT3 inhibition with 4′-bromo-resveratrol significantly decreases tumor volume and weight in melanoma PDX models.\"}]","Mechanistic and preclinical evaluation of SIRT3 as a therapeutic target in melanoma | PDF",1790109338,53]