[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-356693-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-356693-en":131},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","usp4-promotes-non-small-cell-lung-cancer-tumorigenesis-by-antagonizing-cnot4-mediated-degradation-of-paf1","USP4 promotes non-small cell lung cancer tumorigenesis by antagonizing CNOT4-mediated degradation of PAF1","","Non-small cell lung cancer (NSCLC) drives substantial cancer mortality, yet the regulatory balance of its key proteins remains incompletely understood. This study tests whether the deubiquitinase USP4 accelerates NSCLC progression by stabilizing PAF1 and counteracting the E3 ligase CNOT4. USP4 and PAF1 levels were analyzed in NSCLC cells and paired tumor tissues, and functional effects were measured with expression modulation, proteasome inhibition, interaction and ubiquitination assays, and xenograft models. USP4 correlates with poorer survival and promotes tumor growth by opposing CNOT4-mediated ubiquitination and degradation of PAF1.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/usp4-promotes-non-small-cell-lung-cancer-tumorigenesis-by-antagonizing-cnot4-mediated-degradation-of-paf1/356693/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/usp4-promotes-non-small-cell-lung-cancer-tumorigenesis-by-antagonizing-cnot4-mediated-degradation-of-paf1/356693.png","ImageObject",300,407,{"name":42,"@type":43},"Quinn Holloway","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-02","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",13,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is the main question of the study?","Question",{"text":63,"@type":64},"The study examines whether the deubiquitinase USP4 promotes NSCLC progression by stabilizing PAF1 and opposing the E3 ligase CNOT4-mediated degradation.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How did the researchers assess the USP4–PAF1 relationship?",{"text":68,"@type":64},"They measured USP4 and PAF1 expression in NSCLC cells and paired tumor tissues, and used protein interaction and ubiquitination analyses, including K48-linked ubiquitin modification.",{"name":70,"@type":61,"acceptedAnswer":71},"What did the functional experiments show?",{"text":72,"@type":64},"USP4 promoted NSCLC cell proliferation and restored tumor growth, including rescue of CNOT4-induced PAF1 degradation, indicating an antagonistic role in tumorigenesis.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},356693,1790815296,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146},2336474466712,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Chen et al. Respiratory Research (2026) 27:187 [https://doi.org/10.1186/s12931-026-03630-5](https://doi.org/10.1186/s12931-026-03630-5)  \nRespiratory Research  \nRESEARCH Open Access  \nUSP4 promotes non-small cell lung cancer tumorigenesis by antagonizing CNOT4-mediated degradation of PAF1  \nShaomu Chen1†, Yuxuan Wang1†, Song Han2* and Biao Zhang3*  \nAbstract  \nBackground Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality. This study examines whether the deubiquitinase USP4 promotes NSCLC progression by stabilizing PAF1 and opposing the E3 ligase CNOT4 . Methods USP4 and PAF1 expression were examined in NSCLC cell lines and paired tumor tissues by Western blotting and RT-qPCR. Functional studies included USP4 overexpression or silencing, proteasome inhibition, and rescue assays with PAF1 . Co-immunoprecipitation and ubiquitination analyses were performed to confirm protein interaction and K48-linked ubiquitin modification. Cellular proliferation was assessed using CCK-8 assays, and the oncogenic role of USP4 in vivo was evaluated through A549 xenograft models co-expressing USP4 and/or CNOT4, followed by histological and Ki-67 analyses.  \nResults USP4 and PAF1 were concomitantly upregulated in NSCLC cells and tissues, displaying a strong positive correlation. In addition, in-silico analysis of available NSCLC datasets showed that high USP4 or PAF1 expression was associated with poorer overall survival, whereas high CNOT4 expression was associated with better overall survival. USP4 enhanced PAF1 protein stability by directly binding and reducing its K48-linked polyubiquitination, independent of transcriptional regulation. Functionally, USP4 promoted NSCLC cell proliferation and rescued CNOT4-induced PAF1 degradation. In vivo, USP4 expression restored tumor growth and proliferation suppressed by CNOT4, confirming its antagonistic role in tumorigenesis.  \nConclusion USP4 stabilizes PAF1 by counteracting CNOT4-mediated ubiquitination and degradation, thereby promoting NSCLC progression.  \nKeywords USP4, CNOT4, PAF1, ubiquitination, non-small cell lung cancer  \n†Shaomu Chen andYuxuan Wang contributed equally to this work.  \n*Correspondence:  \nSong Han [hansnail@outlook.com](hansnail@outlook.com)[ ](hansnail@outlook.com)Biao Zhang [maxzhang@suda.edu.cn](maxzhang@suda.edu.cn)  \n1Department of Thoracic Surgery, the First Affiliated Hospital of Soochow University, No.899 Pinghai Road, Suzhou, Jiangsu 215006, China 2Department of Thoracic Surgery, the Affiliated Hospital of Medical School, Suzhou Hospital, Nanjing University, No.1 Lijiang Road, Suzhou, Jiangsu 215153, China  \n3Institute of Thoracic Surgery, the First Affiliated Hospital of Soochow University, No. 188 Shizi Road, Suzhou, Jiangsu 215006, China  \n© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/licenses/by-nc-nd/4.0/](vecommons.org/licenses/by-nc-nd/4.0/.)[.](vecommons.org/licenses/by-nc-nd/4.0/.)  \nChen et al. Respiratory Research (2026) 27:187  \nIntroduction  \nLung cancer ranks a","cbCaijZdHBX0F0We","https://ap.wps.com/l/cbCaijZdHBX0F0We","pdf",4130734,11,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusion\n# Introduction","[{\"question\":\"What is the main question of the study?\",\"answer\":\"The study examines whether the deubiquitinase USP4 promotes NSCLC progression by stabilizing PAF1 and opposing the E3 ligase CNOT4-mediated degradation.\"},{\"question\":\"How did the researchers assess the USP4–PAF1 relationship?\",\"answer\":\"They measured USP4 and PAF1 expression in NSCLC cells and paired tumor tissues, and used protein interaction and ubiquitination analyses, including K48-linked ubiquitin modification.\"},{\"question\":\"What did the functional experiments show?\",\"answer\":\"USP4 promoted NSCLC cell proliferation and restored tumor growth, including rescue of CNOT4-induced PAF1 degradation, indicating an antagonistic role in tumorigenesis.\"}]","USP4 promotes non-small cell lung cancer tumorigenesis by antagonizing CNOT4-mediated degradation of PAF1 | PDF",1790126825,28]