[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-detail-370847-en":59,"doc-seo-370847-105":81},{"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":5,"data":60},{"doc_id":61,"user_id":62,"nickname":63,"user_avatar":64,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":66,"doc_content":67,"file_id":68,"file_url":69,"file_type":70,"file_size":71,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":72,"language":73,"language_code":74,"site_id":75,"html_lang":74,"table_of_contents":76,"faqs":77,"seo_title":78,"seo_description":66,"update_tm":79,"read_time":80},370847,1236954412713,"McGucket","https://us-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","FEN1 plays a key role in the transition from HSIL to CSCC","FEN1 plays a key role in the molecular progression from high-grade squamous intraepithelial lesion (HSIL) to invasive cervical squamous cell carcinoma (CSCC), driven by persistent high-risk human papillomavirus (HPV) infection. HSIL and CSCC gene expression datasets were analyzed using WGCNA, GO/KEGG enrichment, immune microenvironment assessment via CIBERSORT, ROC and survival testing, and protein interaction studies linking FEN1 to PCNA. In vitro experiments show FEN1 overexpression, immune-infiltration imbalance, immune escape risk, reduced immune-checkpoint sensitivity, and suppressed proliferation after FEN1 knockdown, identifying FEN1 as a biomarker and therapeutic target.","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \nFEN1 plays a key role in the transition from HSIL toCSCC  \nFengxian Zhang1,5, Xiaomei Chen1,5, Chenyang Chu1,5, Meilin Chen1,5, Ying Yang1, Yanting You1, Jie Zhou1, Pingping Jiang2, Ni Song3􀀍, Yunhong Yu4􀀍 & Yanyan Liu1􀀍  \nCervical high-grade squamous intraepithelial lesion (HSIL) is a well-recognized precursor to cervical squamous cell carcinoma (CSCC). This study aims to explore molecular mechanisms underlying this transition. The datasets of HSIL and CSCC were downloaded from gene expression omnibus database (GEO). HSIL and CSCC coexpression modules were analyzed by Weighted gene coexpression network analysis (WGCNA). Enrichment analysis were analyzed by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG). The immune microenvironment (TIME) was analyzed by CIBERSORT. Receiver operating characteristic (ROC) curve, and survival analysis were performed. The binding of FEN1 and its upstream regulator PCNA was determined by protein interaction, correlation analysis and rigid docking. Immune infiltration, immune checkpoint and docking with small molecule inhibitors was also analyzed. In vitro experiments were conducted to investigate the function and underlying mechanisms of FEN1 in HSIL and CSCC. A total of 30 sequentially expressed shared genes were identified as potential drug targets. Immune infiltration revealed an imbalance of M1/ M2 macrophages, T γδ cells and T cells CD4 memory resting were negatively associated with tumor progression, forming a pro-cancer effect at the HSIL stage and progressing toward CSCC. The key gene FEN1 was over-expressed in HSIL and CSCC, and correlated with the prognosis of CSCC (P \u003C 0.05) . FEN1 interacts with PCNA to regulate macrophage-mediated immune infiltration, increase the risk of immune escape, and decrease the sensitivity to immune checkpoints. Small molecule inhibitor binds to FEN1 docking and inhibits its regulation. FEN1 expression is upregulated in both HSIL and CSCC, with a more pronounced increase in CSCC. Knockdown of FEN1 significantly inhibits the proliferation of cervical cancer cells. This study identifies FEN1 as a biomarker and therapeutic target to truncate or reverse CSCC progression at the HSIL stage.  \nKeywords High-grade squamous intraepithelial lesion, Cervical squamous cell carcinoma, Immune infiltration, Potential biomarker, Flap endonuclease 1  \nAbbreviations  \nAUC Area under curve  \nCSCC Cervical squamous cell carcinoma DEGs Differential expression genes GO Gene ontology  \nGSEA Gene set enrichment analysis HPV High-risk human papillomavirus  \nHSIL High-grade squamous intraepithelial lesion HPA Human protein atlas  \nROC Receiver operating characteristic  \nThis study focuses on the molecular mechanisms underlying the progression from high-grade squamousintraepithelial lesions (HSIL, Table 1) to invasive cervical squamous cell carcinoma (CSCC) driven by persistent high-risk human papillomavirus (HPV) infection. As the fourth most common malignancy in women worldwide, cervical cancer is projected to cause 13,960 new cases and 4310 deaths in the United States in 2023,  \n1School of Traditional Chinese Medicine, Southern Medical University, Baiyun District, Guangzhou 510515, China.  \n2Department of Traditional Chinese Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China. 3The First Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou 510405, China. 4Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Southern Medical University, Guangzhou 510080, China. 5Fengxian Zhang, Xiaomei Chen, Chenyang Chu, and Meilin Chen have contributed equally to this work. 􀀍 email: [1songsun@163.com](1songsun@163.com);  \n[yuyunhong123@126.com](yuyunhong123@126.com); [Liuyyan90@163.com](Liuyyan90@163.com)  \n[www. nature.com/scientificreports/](www. nature.","cbCailbd4w99iu63","https://ap.wps.com/l/cbCailbd4w99iu63","pdf",3859304,18,"English","en",105,"# Background\n# Methods\n## Network and enrichment analyses\n## Immune microenvironment and statistics\n## Interaction and docking\n## Experimental validation\n# Results\n## Shared sequential genes and immune infiltration patterns\n## Prognostic value and immune escape mechanisms\n## Small-molecule inhibitor docking and FEN1 knockdown effects\n# Conclusion","[{\"question\":\"What clinical transition does the study focus on?\",\"answer\":\"The study focuses on progression from HSIL to invasive CSCC, a pathway strongly associated with persistent high-risk HPV infection.\"},{\"question\":\"How was FEN1 linked to immune-related mechanisms?\",\"answer\":\"FEN1 was analyzed for interactions with PCNA and associated with immune microenvironment changes, including macrophage imbalance and immune escape-related effects.\"},{\"question\":\"What experimental evidence supports FEN1 as a therapeutic target?\",\"answer\":\"In vitro knockdown of FEN1 significantly inhibits proliferation of cervical cancer cells, supporting its functional role during HSIL-to-CSCC progression.\"}]","FEN1 plays a key role in the transition from HSIL to CSCC | PDF",1790190674,45,{"code":4,"msg":82,"data":83},"ok",{"site_id":75,"language":74,"slug":84,"title":65,"keywords":85,"description":66,"schema_data":86,"social_meta":140,"head_meta":142,"extra_data":144,"updated_unix":145},"fen1-plays-a-key-role-in-the-transition-from-hsil-to-cscc","",{"@graph":87,"@context":139},[88,102,122],{"@type":89,"itemListElement":90},"BreadcrumbList",[91,95,97,100],{"item":92,"name":93,"@type":94,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":96,"name":9,"@type":94,"position":14},"https://docshare.wps.com/document/",{"item":98,"name":35,"@type":94,"position":99},"https://docshare.wps.com/document/healthcare/",3,{"item":101,"name":65,"@type":94,"position":19},"https://docshare.wps.com/document/fen1-plays-a-key-role-in-the-transition-from-hsil-to-cscc/370847/",{"url":101,"name":65,"@type":103,"image":104,"author":109,"headline":65,"publisher":111,"fileFormat":114,"inLanguage":74,"description":66,"dateModified":115,"datePublished":116,"encodingFormat":114,"isAccessibleForFree":117,"interactionStatistic":118},"DigitalDocument",{"url":105,"@type":106,"width":107,"height":108},"https://docshare.wps.com/thumbnails/fen1-plays-a-key-role-in-the-transition-from-hsil-to-cscc/370847.png","ImageObject",300,407,{"name":63,"@type":110},"Person",{"url":92,"name":112,"@type":113},"DocShare","Organization","application/pdf","2026-11-02","2026-09-23",true,{"@type":119,"interactionType":120,"userInteractionCount":52},"InteractionCounter",{"@type":121},"ViewAction",{"@type":123,"mainEntity":124},"FAQPage",[125,131,135],{"name":126,"@type":127,"acceptedAnswer":128},"What clinical transition does the study focus on?","Question",{"text":129,"@type":130},"The study focuses on progression from HSIL to invasive CSCC, a pathway strongly associated with persistent high-risk HPV infection.","Answer",{"name":132,"@type":127,"acceptedAnswer":133},"How was FEN1 linked to immune-related mechanisms?",{"text":134,"@type":130},"FEN1 was analyzed for interactions with PCNA and associated with immune microenvironment changes, including macrophage imbalance and immune escape-related effects.",{"name":136,"@type":127,"acceptedAnswer":137},"What experimental evidence supports FEN1 as a therapeutic target?",{"text":138,"@type":130},"In vitro knockdown of FEN1 significantly inhibits proliferation of cervical cancer cells, supporting its functional role during HSIL-to-CSCC progression.","https://schema.org",{"og:url":101,"og:type":141,"og:title":65,"og:site_name":112,"og:description":66},"article",{"robots":143,"canonical":101},"index,follow",{"doc_id":61,"site_id":75},1790297690]