[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-332673-105":59,"doc-detail-332673-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","targeting-sirtuins-for-cancer-therapy-epigenetics-modifications-and-beyond","Targeting sirtuins for cancer therapy - epigenetics modifications and beyond","","Sirtuins (SIRTs) are NAD+-dependent histone deacetylases and epigenetic regulators within a seven-member family (SIRT1-7). Their isoforms show distinct subcellular localization and catalyze substrate deacetylation, influencing transcription, DNA repair, genome stability, metabolism, and signal transduction. Evidence links SIRTs to both suppression and progression of human cancers, positioning them as therapeutic targets. This review outlines SIRT structure and function, oncogenic associations, and small-molecule activators and inhibitors, including rationale for combination therapies and future drug development.",{"@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/targeting-sirtuins-for-cancer-therapy-epigenetics-modifications-and-beyond/332673/",{"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/targeting-sirtuins-for-cancer-therapy-epigenetics-modifications-and-beyond/332673.png","ImageObject",300,407,{"name":92,"@type":93},"Sage","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-25","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What are sirtuins (SIRTs) and why are they important in epigenetics?","Question",{"text":112,"@type":113},"SIRTs are NAD+-dependent histone deacetylases forming a seven-member family. They deacetylate histone and non-histone substrates, modulating key biological processes that underlie epigenetic regulation.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How are SIRTs distributed in different cellular compartments?",{"text":117,"@type":113},"SIRT1 and SIRT2 are mainly found in the nucleus and cytoplasm, while SIRT3, SIRT4, and SIRT5 localize to mitochondria. SIRT6 and SIRT7 are distributed in the nucleus.",{"name":119,"@type":110,"acceptedAnswer":120},"How do SIRTs connect to cancer therapy?",{"text":121,"@type":113},"Accumulating evidence indicates SIRTs can both suppress and promote various human cancers. Because of this multifaceted involvement, SIRTs are considered promising therapeutic targets, including through small-molecule activators and inhibitors.","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},332673,1790827366,{"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":52,"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},687197207057,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Review  \nIvyspring  \nInternational Publisher  \nTheranostics  \n2024; 14(17): 6726-6767. doi: 10.7150/thno.100667  \nTargeting sirtuins for cancer therapy: epigenetics modifications and beyond  \nHui Shen1,\\#, Xinyi Qi2,3,\\#, Yue Hu1,\\#, Yi Wang3,4, Jin Zhang3,􀀍, Zhongyu Liu4,􀀍, Zheng Qin1,􀀍  \n1. Department of Respiratory and Critical Care Medicine, Department of Outpatient, The First Hospital of China Medical University, Shenyang 110001, China.  \n2. Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.  \n3. School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, China.  \n4. No. 989 Hospital of Joint Logistic Support Force of PLA, Luoyang 471031, China.  \n\\#These authors contributed equally to this work.  \n􀀍 Corresponding authors: Zheng Qin, Email: [qinzheng@cmu1h.com](qinzheng@cmu1h.com); Zhongyu Liu, [Email: 370167547@qq.com](Email: 370167547@qq.com); Jin Zhang, Email: [zhangjin1989@szu.edu.cn](zhangjin1989@szu.edu.cn).  \n© The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)). See [http://ivyspring.com/terms](http://ivyspring.com/terms) for full terms and conditions.  \nReceived: 2024.07.08; Accepted: 2024.09.29; Published: 2024.10.14  \nAbstract  \nSirtuins (SIRTs) are well-known as nicotinic adenine dinucleotide+(NAD+)-dependent histone deacetylases, which are important epigenetic enzymes consisting of seven family members (SIRT1-7). Of note, SIRT1 and SIRT2 are distributed in the nucleus and cytoplasm, while SIRT3, SIRT4 and SIRT5 are localized in the mitochondria. SIRT6 and SIRT7 are distributed in the nucleus. SIRTs catalyze the deacetylation of various substrate proteins, thereby modulating numerous biological processes, including transcription, DNA repair and genome stability, metabolism, and signal transduction. Notably, accumulating evidence has recently underscored the multi-faceted roles of SIRTs in both the suppression and progression of various types of human cancers. Crucially, SIRTs have been emerging as promising therapeutic targets for cancer therapy. Thus, in this review, we not only present an overview of the molecular structure and function of SIRTs, but elucidate their intricate associations with oncogenesis. Additionally, we discuss the current landscape of small-molecule activators and inhibitors targeting SIRTsin the contexts of cancer and further elaborate their combination therapies, especially highlighting their prospective utility for future cancer drug development.  \nKeywords: Sirtuin (SIRT); Epigenetics modification; Cancer therapy; Small-molecule activator; Small-molecule inhibitor  \nIntroduction  \nSirtuins (SIRTs) are NAD+-dependent histone deacetylases (HDACs) . SIRTs were first discovered and characterized in Saccharomyces cerevisiae and named the yeast silent information regulator 2 (Sir2), whose mammalian homologue is known as Sirt [1, 2] . Other isoforms were later found in other species of bacteria, plants and mammals. HDACs are enzymes that eliminate acetyl groups from the lysine residues of histone and non-histone proteins. There are 18 known HDAC enzymes, which are divided into four major classes: Class I Rpd3-like proteins (HDAC1, HDAC2, HDAC3, and HDAC8); Class II Hda1-like proteins (HDAC4, HDAC5, HDAC6, HDAC7, HDAC9, and HDAC10); and Class III Sir2-like proteins (SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6,  \nand SIRT7); and class IV proteins (HDAC11) . In mammals the SIRTs family belongs to the evolutionary conserved proteins of class III histone deacetylases (HDAC) with seven members (SIRT1-SIRT7) (Figure 1A) [2] . Around 275 amino acid residues make up the highly conserved central catalytic structural domain of SIRTs, which is encircled by structural domains at the C- and N-t","cbCaiftZHE5aAWBQ","https://ap.wps.com/l/cbCaiftZHE5aAWBQ","pdf",10236461,42,"English","# Abstract\n# Introduction\n## Sirtuins as NAD+-dependent histone deacetylases\n## HDAC classification and SIRT family characteristics\n## Subcellular localization and functional implications\n## Histone acetylation–deacetylation in epigenetic regulation\n# Figures","[{\"question\":\"What are sirtuins (SIRTs) and why are they important in epigenetics?\",\"answer\":\"SIRTs are NAD+-dependent histone deacetylases forming a seven-member family. They deacetylate histone and non-histone substrates, modulating key biological processes that underlie epigenetic regulation.\"},{\"question\":\"How are SIRTs distributed in different cellular compartments?\",\"answer\":\"SIRT1 and SIRT2 are mainly found in the nucleus and cytoplasm, while SIRT3, SIRT4, and SIRT5 localize to mitochondria. SIRT6 and SIRT7 are distributed in the nucleus.\"},{\"question\":\"How do SIRTs connect to cancer therapy?\",\"answer\":\"Accumulating evidence indicates SIRTs can both suppress and promote various human cancers. Because of this multifaceted involvement, SIRTs are considered promising therapeutic targets, including through small-molecule activators and inhibitors.\"}]","Targeting sirtuins for cancer therapy - epigenetics modifications and beyond | PDF",1789999039,106]