[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-331704-105":59,"doc-detail-331704-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","molecular-sentinels-unveiling-the-role-of-sirtuins-in-prostate-cancer-progression-review","Molecular Sentinels: Unveiling the Role of Sirtuins in Prostate Cancer Progression - Review","","Prostate cancer remains a critical global health challenge marked by high mortality and marked heterogeneity, especially in advanced disease. Early-stage tumors are often manageable, yet metastatic prostate cancer shows strong treatment resistance, creating an urgent demand for precise biomarkers and novel therapies. This review examines sirtuins—NAD+-dependent histone deacetylases—whose context-dependent functions can drive either tumor suppression or progression. It links sirtuins to key cancer hallmarks including growth control escape, invasion and metastasis, apoptosis resistance, angiogenesis, and replicative immortality, with an emphasis on individual SIRT members as biomarker and therapeutic targets.",{"@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/molecular-sentinels-unveiling-the-role-of-sirtuins-in-prostate-cancer-progression-review/331704/",{"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/molecular-sentinels-unveiling-the-role-of-sirtuins-in-prostate-cancer-progression-review/331704.png","ImageObject",300,407,{"name":92,"@type":93},"Aurelia","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What problem does the review address about prostate cancer progression?","Question",{"text":112,"@type":113},"It addresses prostate cancer’s high mortality and heterogeneity, noting that advanced or metastatic disease is often resistant to existing treatments and requires improved biomarkers and therapies.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do sirtuins influence prostate cancer according to the review?",{"text":117,"@type":113},"Sirtuins have dualistic, context-dependent roles, contributing either to tumor suppression or to progression by affecting multiple cancer hallmarks.",{"name":119,"@type":110,"acceptedAnswer":120},"Which sirtuins are highlighted as having specific roles in prostate cancer?",{"text":121,"@type":113},"The review emphasizes SIRT1, SIRT3, SIRT4, SIRT2, SIRT6, SIRT5, and SIRT7, describing distinct mechanisms such as chemoresistance, metabolic regulation, immune modulation, DNA repair, invasion, and metabolic stress adaptation.","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},331704,1790876014,{"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":39,"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},1099514068365,"https://ap-avatar.wpscdn.com/avatar/10000253d8d9f28188e?x-image-process=image/resize,m_fixed,w_180,h_180&k=1794309523707217728","Review  \nMolecular Sentinels: Unveiling the Role of Sirtuins in Prostate Cancer Progression  \nSurbhi Chouhan 1,2, *, Naoshad Muhammad 3, Darksha Usmani 4, Tabish H. Khan 5 and Anil Kumar 6  \nAcademic Editor: Atsushi Matsuzawa  \nReceived: 15 November 2024  \nRevised: 21 December 2024  \nAccepted: 27 December 2024  \nPublished: 28 December 2024  \nCitation: Chouhan, S.; Muhammad, N.; Usmani, D.; Khan, T.H.; Kumar, A. Molecular Sentinels: Unveiling the Role of Sirtuins in Prostate Cancer Progression. Int. J. Mol. Sci. 2025, 26, 183. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms26010183  \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://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \n1 Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA  \n2 Cecil H and Ida Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA  \n3 Department of Radiation Oncology, School of Medicine, Washington University, St. Louis, MO 63130, USA  \n4 Department of Ophthalmology, Washington University School of Medicine, St. Louis, MO 63130, USA  \n5 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63130, USA  \n6 Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA  \n* Correspondence: [surbhi.chouhan@utsouthwestern.edu](surbhi.chouhan@utsouthwestern.edu)  \nAbstract: Prostate cancer (PCa) remains a critical global health challenge, with high mortality rates and significant heterogeneity, particularly in advanced stages. While early-stage PCa is often manageable with conventional treatments, metastatic PCa is notoriously resistant, highlighting an urgent need for precise biomarkers and innovative therapeutic strategies. This review focuses on the dualistic roles of sirtuins, a family of NAD+-dependent histone deacetylases, dissecting their unique contributions to tumor suppression or progression in PCa depending on the cellular context. It reveals their multifaceted impact on hallmark cancer processes, including sustaining proliferative signaling, evading growth suppressors, activating invasion and metastasis, resisting cell death, inducing angiogenesis, and enabling replicative immortality. SIRT1, for example, fosters chemoresistance and castration-resistant prostate cancer through metabolic reprogramming, immune modulation, androgen receptor signaling, and enhanced DNA repair. SIRT3 and SIRT4 suppress oncogenic pathways by regulating cancer metabolism, while SIRT2 and SIRT6 influence tumor aggressiveness and androgen receptor sensitivity, with SIRT6 promoting metastatic potential. Notably, SIRT5 oscillates between oncogenic and tumor-suppressive roles by regulating key metabolic enzymes; whereas, SIRT7 drives PCa proliferation and metabolic stress adaptation through its chromatin and nucleolar regulatory functions. Furthermore, we provide a comprehensive summary of the roles of individual sirtuins, highlighting their potential as biomarkers in PCa and exploring their therapeutic implications. By examining each of these specific mechanisms through which sirtuins impact PCa, this review underscores the potential of sirtuin modulation to address gaps in managing advanced PCa. Understanding sirtuins’ regulatory effects could redefine therapeutic approaches, promoting precision strategies that enhance treatment efficacy and improve outcomes for patients with aggressive disease.  \nKeywords: prostate cancer (PCa); prostatic intraepithelial neoplasia (PINs); sirtuins; histone deacetylase; Janus-faced sirtuin; cancer signaling; immune modulation; chemoresistance; targeted chemotherapy  \n1. Introduction ","cbCaicArjRYX7Own","https://ap.wps.com/l/cbCaicArjRYX7Own","pdf",2866577,36,"English","# Abstract\n# Introduction\n# Sirtuins as Dualistic Regulators in Prostate Cancer\n## SIRT1-related mechanisms\n## SIRT3/SIRT4 roles\n## SIRT2/SIRT6 and androgen receptor sensitivity\n## SIRT5 metabolic enzyme regulation\n## SIRT7 proliferation and metabolic stress adaptation\n# Therapeutic and Biomarker Implications","[{\"question\":\"What problem does the review address about prostate cancer progression?\",\"answer\":\"It addresses prostate cancer’s high mortality and heterogeneity, noting that advanced or metastatic disease is often resistant to existing treatments and requires improved biomarkers and therapies.\"},{\"question\":\"How do sirtuins influence prostate cancer according to the review?\",\"answer\":\"Sirtuins have dualistic, context-dependent roles, contributing either to tumor suppression or to progression by affecting multiple cancer hallmarks.\"},{\"question\":\"Which sirtuins are highlighted as having specific roles in prostate cancer?\",\"answer\":\"The review emphasizes SIRT1, SIRT3, SIRT4, SIRT2, SIRT6, SIRT5, and SIRT7, describing distinct mechanisms such as chemoresistance, metabolic regulation, immune modulation, DNA repair, invasion, and metabolic stress adaptation.\"}]","Molecular Sentinels: Unveiling the Role of Sirtuins in Prostate Cancer Progression - Review | PDF",1789994777,91]