[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-345526-105":59,"doc-detail-345526-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","uhrf1-drives-hepatocellular-carcinoma-progression-via-epigenetic-repression-of-sfmbt2","UHRF1 drives hepatocellular carcinoma progression via epigenetic repression of SFMBT2","","Hepatocellular carcinoma (HCC) causes high cancer-related mortality, requiring novel therapeutic targets. This study clarifies how UHRF1 promotes HCC by focusing on epigenetic repression of SFMBT2. Integrating clinical samples, bioinformatics, cell culture assays, and in vivo xenograft models, the work shows UHRF1 is elevated in HCC and associates with advanced grade and poor survival. Mechanistically, UHRF1 binds the SFMBT2 promoter CpG islands to repress SFMBT2, activating ERK/AKT/NF-κB signaling, increasing HOXB13 and transcriptionally stimulating LTK.",{"@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/uhrf1-drives-hepatocellular-carcinoma-progression-via-epigenetic-repression-of-sfmbt2/345526/",{"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/uhrf1-drives-hepatocellular-carcinoma-progression-via-epigenetic-repression-of-sfmbt2/345526.png","ImageObject",300,407,{"name":92,"@type":93},"Levi","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does UHRF1 play in hepatocellular carcinoma progression?","Question",{"text":112,"@type":113},"UHRF1 promotes HCC cell proliferation, migration, and invasion by activating ERK/AKT/NF-κB signaling pathways and by driving epigenetic repression of SFMBT2.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does UHRF1 regulate SFMBT2 at the epigenetic level?",{"text":117,"@type":113},"UHRF1 binds CpG islands in the SFMBT2 promoter and epigenetically represses SFMBT2 expression.",{"name":119,"@type":110,"acceptedAnswer":120},"How does SFMBT2 connect to downstream HOXB13 and LTK activation?",{"text":121,"@type":113},"UHRF1-mediated SFMBT2 downregulation increases HOXB13 expression, and HOXB13 transcriptionally activates LTK, contributing to tumor aggressiveness.","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},345526,1790183735,{"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":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":46,"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":31},7971461740909,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \nUHRF1 drives hepatocellular carcinoma progression via epigenetic repression of SFMBT2  \nZekai Hu1,3, Qi Sun2,3, Weiliang Xia1􀀍 & Zenglei He1􀀍  \nHepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, necessitating the identification of novel therapeutic targets. UHRF1 is an epigenetic regulator implicated in various cancers, but its precise mechanistic role in HCC progression remains incompletely understood. This study investigates the epigenetic mechanisms by which UHRF1 promotes HCC pathogenesis, with a focus on its interaction with SFMBT2. A multifaceted approach integrating clinical sample analysis, bioinformatics, in vitro cell culture experiments, and in vivo xenograft models was employed. UHRF1 expression was assessed in HCC tissues and cell lines. Functional roles were investigated through overexpression and knockdown models, evaluated by MTT, Transwell, and Western blot assays. ChIP and luciferase reporter assays were used to examine promoter binding and transcriptional regulation. UHRF1 was significantly upregulated in HCC tissues and correlated with advanced tumor grade and poor survival. UHRF1 promoted HCC cell proliferation, migration, and invasion by activating the ERK/AKT/NF-κB signaling pathways. Mechanistically, UHRF1 bound toCpG islands in the SFMBT2 promoter, epigenetically repressing its expression. SFMBT2 overexpression reversed UHRF1-drivenoncogenic effects in vitro and in vivo. Furthermore, UHRF1-mediated SFMBT2 downregulation led to increased HOXB13 expression, which transcriptionally activated LTK. This study identifies a novel UHRF1/SFMBT2 epigenetic axis critical for HCC progression. UHRF1 represses SFMBT2 to activate ERK/AKT/NF-κB and HOXB13/LTK pathways, driving tumor aggressiveness. Restoration of SFMBT2 counteracts these effects, highlighting its tumor-suppressive role. These findings position UHRF1 as a promising prognostic biomarker and therapeutic target in HCC.  \nKeywords UHRF1, SFMBT2, Hepatocellular carcinoma, Epigenetics, HOXB13  \nAbbreviations  \nHCC  \nLTKUHRF1 MEG3  \nCSF1 SFMBT2 miRNA TCGAUALCANDMEM qRT-PCRWB  \nChIP  \ncDNAsiRNA HOXB13 IHC  \np-ERK  \nHepatocellular carcinoma Leukocyte tyrosine kinase  \nUbiquitin-like containing PHD and RING finger domain 1 Maternally expressed gene 3  \nColony-stimulating factor 1  \nScm-like with four mbt domains 2  \nmicroRNA  \nThe Cancer Genome Atlas Birmingham cancer data analysis portal Dulbecco’s Modified Eagle Medium  \nQuantitative reverse transcription polymerase chain reaction Western blotting  \nChromatin immunoprecipitation Complementary DNA  \nSmall interfering RNA Homeobox B13  \nImmunohistochemistry  \nPhospho-extracellular signal-regulated kinase  \n1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. 2Hangzhou Ninth People’s Hospital, Hangzhou, Zhejiang, China. 3These authors contributed equally: Zekai Hu and Qi Sun. 􀀍 email: [xiaweiliang@zju.edu.cn](xiaweiliang@zju.edu.cn); [hezenglei@zju.edu.cn](hezenglei@zju.edu.cn)  \n[www. nature.com/scientificreports/](www. nature.com/scientificreports/)  \np-NF-κB Phospho-nuclear factor kappa-B  \nMTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide GEPIA Gene Expression Profiling Interactive Analysis  \nAKT Serine/threonine kinase  \nTXNIP Thioredoxin-interacting protein  \nDNMTs Dysregulated activity of DNA methyltransferases TET Ten-eleven translocation proteins  \nHDACs Hyperactivity of histone deacetylases  \nLiver cancer is now the sixth most common malignancy worldwide and the third leading cause of cancer-related deaths, with hepatocellular carcinoma (HCC) accounting for approximately 75–85% of primary liver cancers1. Epigenetic reprogramming, including aberrant DNA methylation and histone modification, plays a pivotal role in HCC initiation and progression. Besides, non-coding R","cbCaimeZLMrn8Kza","https://ap.wps.com/l/cbCaimeZLMrn8Kza","pdf",3923498,"English","# Background and Rationale\n## Epigenetic regulation in HCC\n## UHRF1 as an epigenetic regulator\n# Methods and Experimental Strategy\n## Clinical samples and expression analysis\n## Cell and animal models\n## Functional assays and signaling readouts\n# Mechanistic Findings\n## UHRF1 represses SFMBT2 through promoter binding\n## Activation of ERK/AKT/NF-κB and downstream effects\n## HOXB13-mediated activation of LTK\n# Conclusions and Implications\n## UHRF1/SFMBT2 axis as a biomarker and target","[{\"question\":\"What role does UHRF1 play in hepatocellular carcinoma progression?\",\"answer\":\"UHRF1 promotes HCC cell proliferation, migration, and invasion by activating ERK/AKT/NF-κB signaling pathways and by driving epigenetic repression of SFMBT2.\"},{\"question\":\"How does UHRF1 regulate SFMBT2 at the epigenetic level?\",\"answer\":\"UHRF1 binds CpG islands in the SFMBT2 promoter and epigenetically represses SFMBT2 expression.\"},{\"question\":\"How does SFMBT2 connect to downstream HOXB13 and LTK activation?\",\"answer\":\"UHRF1-mediated SFMBT2 downregulation increases HOXB13 expression, and HOXB13 transcriptionally activates LTK, contributing to tumor aggressiveness.\"}]","UHRF1 drives hepatocellular carcinoma progression via epigenetic repression of SFMBT2 | PDF",1790057975]