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A dual epigenetic inhibition strategy is proposed to suppress breast cancer growth and metastasis. Small-molecule PRMT1 inhibition downregulates SUV39H1 via enhanced ubiquitination, and co-inhibition produces stronger tumor suppression than either monotherapy. Mechanistically, co-inhibition increases chromatin accessibility, promotes pro-migration regulator expression, elevates CD8+ T and NK infiltration, and upregulates PD-L1, improving anti-PD-L1 antibody responsiveness.",{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/dual-inhibition-of-prmt1-and-suv39h1-suppresses-breast-cancer-progression-and-enhances-immunotherapy-response/353160/",{"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/dual-inhibition-of-prmt1-and-suv39h1-suppresses-breast-cancer-progression-and-enhances-immunotherapy-response/353160.png","ImageObject",300,407,{"name":92,"@type":93},"4398046744996","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why are PRMT1 inhibitors alone limited for breast cancer treatment?","Question",{"text":112,"@type":113},"PRMT1 inhibitors exhibit minimal inhibition of tumor growth when used as monotherapy, despite PRMT1 being dysregulated in many cancers including breast cancer.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does dual inhibition of PRMT1 and SUV39H1 work mechanistically?",{"text":117,"@type":113},"PRMT1 inhibition downregulates SUV39H1 by enhancing its ubiquitination; together they increase chromatin accessibility at promoter regions and boost expression of key regulators involved in cell growth and migration.",{"name":119,"@type":110,"acceptedAnswer":120},"How does the PRMT1/SUV39H1 strategy affect the immune microenvironment and immunotherapy response?",{"text":121,"@type":113},"Dual inhibition increases infiltration of CD8+ T cells and NK cells and upregulates PD-L1. Combining dual inhibition with an anti-PD-L1 antibody further enhances breast cancer responsiveness to immunotherapy.","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},353160,1790169188,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":66,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":138,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},4398046744996,"Ivyspring  \nInternational Publisher  \nInternationalJournal of Biological Sciences  \n2026; 22(11): 6100-6114. doi: 10.7150/ijbs.130955  \nResearch Paper  \nDual inhibition of PRMT1 and SUV39H1 suppresses breast cancer progression and enhances immunotherapy response  \nGe Wang1\\#, Jiagui Song2\\#, Xinwei Duan1, Kunhao Zhou1, Jing Zhang1, Hongquan Zhang1, Yu Yu1􀀍  \n1. Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, PKU International Cancer Institute, Peking University Health Science Center, Beijing 100191, China.  \n2. Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China.  \n\\# These authors contributed equally to this work  \n􀀍 Corresponding author: Yu Yu, Peking University Health Science Center, \\#38 Xue Yuan Rd., Beijing 100191, China. Email: [yuyu@bjmu.edu.cn](yuyu@bjmu.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 [https://ivyspring.com/terms](https://ivyspring.com/terms) for full terms and conditions.  \nReceived: 2026.01.05; Accepted: 2026.05.26; Published: 2026.06.04  \nAbstract  \nProtein arginine methyltransferase 1 (PRMT1) dysregulation is frequently observed in various human cancers, including breast cancer. However, the antitumor efficacy of PRMT1 inhibitors remains limited in the treatment of breast cancer. Here, we propose a dual epigenetic inhibition strategy that effectively suppresses breast cancer growth and metastasis. We demonstrate that GSK3368715, a small-molecule inhibitor of PRMT1, downregulates the protein levels of the histone lysine methyltransferase SUV39H1 by enhancing its ubiquitination. Dual inhibition of PRMT1 and SUV39H1 results in significantly greater suppression of tumor growth and metastasis compared to either monotherapy, supporting the synergistic effects of targeting two epigenetic regulators. Consistently, dual inhibition markedly suppresses the growth of breast cancer organoids relative to single-agent treatments. Mechanistically, co-inhibition of SUV39H1 and PRMT1 enhances chromatin accessibility in promoter regions, thereby promoting the expression of key regulators involved in cell growth and migration. Furthermore, dual inhibition increases infiltration of CD8+ T cells and NK cells and upregulates PD-L1 expression. Importantly, the combination of dual inhibition with anti-PD-L1 antibody enhances the responsiveness of breast cancer to immunotherapy. Taken together, our findings indicate that co-targeting PRMT1 and SUV39H1 represents a promising therapeutic strategy for breast cancer.  \nKeywords: breast cancer; epigenetic inhibitor; PRMT1; SUV39H1; immunotherapy  \nIntroduction  \nProtein arginine methyltransferases (PRMTs) mediate arginine methylation in both histone and non-histone proteins, regulating a wide range of biological processes, including translation, RNA metabolism, DNA damage response, and stem cell maintenance [1-6] . PRMTs are frequently dysregulated in various human cancers [7] . Specific PRMT inhibitors have emerged as promising therapeutic agents for cancer treatment [8, 9], and their combination with other therapeutic modalities may offer clinical benefits to patients [10, 11] . PRMT1  \nis the predominant type I PRMT responsible for catalyzing asymmetric dimethylarginine (ADMA)  \n[12] and accounts for the majority of PRMT activity in mammalian cells. Previous studies have reported that PRMT1 mediates ADMA modification of certain histone methyltransferases, thereby enhancing their protein stability [13] . PRMT1 inhibitors exhibit synergistic effects in suppressing tumor growth when combined with other small-molecule inhibitors [14, 15] . Pharmacological inhibition of PRMT1 in combination with chemotherapy gemcitabine has a  \nsynergistic effect on pancreatic tumor growth [16]","cbCaimWyAkBsA31B","https://ap.wps.com/l/cbCaimWyAkBsA31B","pdf",34109838,15,"English","# Abstract\n# Keywords\n# Introduction","[{\"question\":\"Why are PRMT1 inhibitors alone limited for breast cancer treatment?\",\"answer\":\"PRMT1 inhibitors exhibit minimal inhibition of tumor growth when used as monotherapy, despite PRMT1 being dysregulated in many cancers including breast cancer.\"},{\"question\":\"How does dual inhibition of PRMT1 and SUV39H1 work mechanistically?\",\"answer\":\"PRMT1 inhibition downregulates SUV39H1 by enhancing its ubiquitination; together they increase chromatin accessibility at promoter regions and boost expression of key regulators involved in cell growth and migration.\"},{\"question\":\"How does the PRMT1/SUV39H1 strategy affect the immune microenvironment and immunotherapy response?\",\"answer\":\"Dual inhibition increases infiltration of CD8+ T cells and NK cells and upregulates PD-L1. Combining dual inhibition with an anti-PD-L1 antibody further enhances breast cancer responsiveness to immunotherapy.\"}]","Dual inhibition of PRMT1 and SUV39H1 suppresses breast cancer progression and enhances immunotherapy response | PDF",1790103348,38]