[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-332826-105":59,"doc-detail-332826-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","transcriptional-and-functional-regulation-of-cell-cycle-and-uv-response-by-ppar-in-human-skin-epidermal-cells","Transcriptional and functional regulation of cell cycle and UV response by PPARβ in human skin epidermal cells","","Solar radiation drives human exposure to UV, a major skin-cancer carcinogen through DNA damage. Skin cells limit tumor development by activating the DNA damage response (DDR) to preserve genome integrity. Peroxisome proliferator-activated receptor beta (PPARβ) is a druggable transcription factor linked to UV-dependent skin cancers, yet its mechanism in human epidermis remains unclear. Results show PPARβ directly controls gene expression programs for cell cycle and DNA repair in normal human epidermal keratinocytes, reducing proliferation, inducing G2/M arrest, and disrupting ATR pathway activity, thereby increasing UV-induced apoptosis. Using a mouse melanoma model, PPARβ depletion reduces melanoma tumorigenicity and delays tumor formation, supporting PPARβ inhibition as a prevention strategy.",{"@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/transcriptional-and-functional-regulation-of-cell-cycle-and-uv-response-by-ppar-in-human-skin-epidermal-cells/332826/",{"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/transcriptional-and-functional-regulation-of-cell-cycle-and-uv-response-by-ppar-in-human-skin-epidermal-cells/332826.png","ImageObject",300,407,{"name":92,"@type":93},"Evangeline","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-04","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How does PPARβ influence UV-induced DNA damage responses in human keratinocytes?","Question",{"text":112,"@type":113},"Loss of PPARβ disrupts expression and activation of the ATR pathway, a critical DDR component for responding to UV-induced DNA damage. This disruption likely contributes to an increased apoptotic response after UV exposure.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What effects does PPARβ loss have on the cell cycle of human epidermal keratinocytes?",{"text":117,"@type":113},"PPARβ loss downregulates key cell cycle regulators, including cyclins and CDKs, while upregulating p21, a CDK inhibitor. These changes reduce proliferation and induce cell cycle arrest at the G2/M phase.",{"name":119,"@type":110,"acceptedAnswer":120},"What do the mouse melanoma model results suggest about targeting PPARβ for skin cancer prevention?",{"text":121,"@type":113},"In the mouse melanoma model, depleting PPARβ decreases melanoma tumorigenicity and delays tumor formation. The findings support PPARβ inhibition as a potential therapeutic target to prevent UV-induced skin cancers by regulating proliferation.","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},332826,1790173925,{"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":52,"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,"preview_page_count":4},13056703019662,"https://ap-avatar.wpscdn.com/avatar/be000253a8e92610077?_k=1778726343310543188","DOI: 10.1096/fj.202401950R  \nRESEAR CH ARTICLE  \nTranscriptional and functional regulation of cell cycle and UV response by PPARβ in human skin epidermal cells  \nThanhNhan Nguyen  | Carine Winkler | Stefanie Ginster | Stéphanie Claudinot  | Liliane Michalik  | Paris Jafari   \nCenter for Integrative Genomics, University of Lausanne, Lausanne, Switzerland  \nCorrespondence  \nParis Jafari, Centre for Integrative Genomics (CIG), University of Lausanne, UNIL-Sorge Génopode Building, CH-1015 Lausanne, Switzerland. [Email:](Email: paris.jafari@unil.ch)[ paris.jafari@unil.ch](Email: paris.jafari@unil.ch)  \nAbstract  \nSolar radiation is the main source of human exposure to UV rays, which is the major carcinogen in skin cancers by inducing DNA damage. Skin cells repair these damages by activating the DNA damage response (DDR) to safeguard genome integrity, thereby preventing skin cancers. Peroxisome proliferatoractivated receptor beta (PPARβ), a druggable transcription factor, is involved in the development of UV-dependent skin cancers, although its role is not mechanistically elucidated. We showed previously that PPARβ knockout (KO) mice are less prone to UV-induced skin cancers. Here, we report that PPARβ directly regulates gene expression programs associated with cell cycle and DNA repair pathways in normal human epidermal keratinocytes (NHEK) . The loss of function of PPARβ in human keratinocytes led to a downregulation in the expression of key cell cycle regulators, including cyclins and cyclin-dependent kinases (CDKs) . Simultaneously, it upregulated the expression of p21 protein, a known CDK inhibitor. These molecular alterations resulted in a significant reduction in cell proliferation and induced cell cycle arrest at the G2/M phase. Moreover, the absence of functional PPARβ disrupted the expression and activation of the ataxia telangiectasia and Rad3-related (ATR) pathway, a critical component of the cellular response to UV-induced DNA damage. The alterations in the ATR pathway likely contributed to an increased apoptotic response of NHEK to UV radiation. Using a mouse melanoma model, we demonstrated that the depletion of PPARβ decreases tumorigenicity of melanoma cells and delays tumor formation. Our data suggest that PPARβ inhibition could be considered as a therapeutic target for the prevention of UV-induced skin cancers, by regulating cell proliferation,  \nAbbreviations: ATM, ataxia telangiectasia mutated; ATR, ataxia telangiectasia and Rad3-related; CDK, cyclin-dependent kinase; CDKN1A,  \ncyclin-dependent kinase inhibitor 1A; CDKs, cyclin-dependent kinases; CHK1, checkpoint kinase 1; CPD, cyclobutane pyrimidine dimer; DDR, DNA damage response; DEG, differentially expressed gene; ELISA, enzyme-linked immunosorbent assay; FA/BRC, Fanconi anemia/BRCA; FDR, false discovery rate; GSEA, gene set enrichment analysis; HKGS, human keratinocyte growth supplement; HR, homologous recombination; KO, knockout; MCM, minichromosome maintenance protein complex; MSigDB, molecular signatures database; NER, nucleotide excision repair; NHEK, human epidermal keratinocytes; PCNA, proliferating cell nuclear antigen; PCR, polymerase chain reaction; PPAR, peroxisome proliferator-activated receptor; SCC, squamous cell carcinoma; UV, ultraviolet; VSMC, human vascular smooth muscle cells.  \nThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.  \n© 2024 The Author(s) . The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.  \n1 | INTRODUCTION  \nattenuating DDR, and eliminating skin cells with high UV-induced mutational burden.  \nKEYWORDS  \ncell cycle, DNA damage response, keratinocyte, PPARβ, skin cancer, squamous cell carcinoma and UV  \nfor oncogenic transform","cbCaiddXCCbRGJ87","https://ap.wps.com/l/cbCaiddXCCbRGJ87","pdf",5995577,"English","# Abstract\n# Introduction\n## UV-induced DNA damage and DDR activation\n## ATR/CHK1 signaling and cell fate\n## PPARβ as a regulator in skin cells","[{\"question\":\"How does PPARβ influence UV-induced DNA damage responses in human keratinocytes?\",\"answer\":\"Loss of PPARβ disrupts expression and activation of the ATR pathway, a critical DDR component for responding to UV-induced DNA damage. This disruption likely contributes to an increased apoptotic response after UV exposure.\"},{\"question\":\"What effects does PPARβ loss have on the cell cycle of human epidermal keratinocytes?\",\"answer\":\"PPARβ loss downregulates key cell cycle regulators, including cyclins and CDKs, while upregulating p21, a CDK inhibitor. These changes reduce proliferation and induce cell cycle arrest at the G2/M phase.\"},{\"question\":\"What do the mouse melanoma model results suggest about targeting PPARβ for skin cancer prevention?\",\"answer\":\"In the mouse melanoma model, depleting PPARβ decreases melanoma tumorigenicity and delays tumor formation. The findings support PPARβ inhibition as a potential therapeutic target to prevent UV-induced skin cancers by regulating proliferation.\"}]","Transcriptional and functional regulation of cell cycle and UV response by PPARβ in human skin epidermal cells | PDF",1789999652]