[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-378317-105":59,"doc-detail-378317-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","preservation-of-circadian-rhythm-in-hepatocellular-cancer","Preservation of circadian rhythm in hepatocellular cancer","","Circadian rhythms are driven by a molecular clock that regulates thousands of tissue-specific genes through transcription–translation–degradation feedback. To examine how rhythmicity changes in cancer, this study analyzes genome-wide circadian rhythmic gene expression in a mouse liver-cancer model induced by diethylnitrosamine. Tumor-bearing and control mice received cisplatin every 2 hours across a 24-hour cycle, with gene expression measured using XR-seq. Rhythmic clock gene expression appears in both healthy liver and tumors, with tumors showing robust amplitudes and a modest phase advance and only ~10% overlap in rhythmic genes, suggesting time-dependent opportunities for anticancer chronotherapy.",{"@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/preservation-of-circadian-rhythm-in-hepatocellular-cancer/378317/",{"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/preservation-of-circadian-rhythm-in-hepatocellular-cancer/378317.png","ImageObject",300,407,{"name":92,"@type":93},"supergirl","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-24",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 is circadian rhythmicity regulated at the cellular level in this study?","Question",{"text":112,"@type":113},"It is controlled by a molecular clock involving core clock genes/proteins that operate through a transcription–translation–degradation feedback loop, generating daily rhythms and regulating downstream circadian-controlled genes.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did the researchers measure gene expression rhythms in tumor and control mice?",{"text":117,"@type":113},"Mice received cisplatin every 2 hours over a 24-hour cycle, then were sacrificed 2 hours after each injection; gene expression was assessed genome-wide using the XR-seq assay.",{"name":119,"@type":110,"acceptedAnswer":120},"What key differences in circadian rhythmic genes were found between healthy liver and tumors?",{"text":121,"@type":113},"Clock genes show robust rhythmic amplitudes in tumors with a modest phase advance, yet only about 10% overlap exists between rhythmic genes in normal and cancerous cells, and tumor-only rhythmic genes peak mainly in daytime hours.","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},378317,1790449656,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"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":52,"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},962088121634,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","RESEARCH ARTICLE EDITORS’ PICK   \nPreservation of circadian rhythm in hepatocellular cancer  \nReceived for publication, June 16, 2023, and in revised form, August 18, 2023 Published, Papers in Press, September 14, 2023, [https://doi.org/10.1016/j.jbc.2023.105251](https://doi.org/10.1016/j.jbc.2023.105251)  \nYanyan Yang‡, Ashraf N. Abdo‡, Hiroaki Kawara‡, Christopher P. Selby, and Aziz Sancar*  \nFrom the Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA  \nReviewed by members of the JBC Editorial Board. Edited by Eric Fearon  \nCircadian rhythms are controlled at the cellular level by a molecular clock consisting of several genes/proteins engaged ina transcription–translation–degradation feedback loop. These core clock proteins regulate thousands of tissue-specific genes. Regarding circadian control in neoplastic tissues, reports to date have demonstrated anomalous circadian function in tumor models and cultured tumor cells. We have extended these studies by analyzing circadian rhythmicity genome-wide in a mouse model of liver cancer, in which mice treated with diethylnitrosamine at 15 days develop liver tumors by 6 months. We injected tumor-bearing and control tumor-free mice with cisplatin every 2 h over a 24-h cycle; 2 h after each injection mice were sacrificed and gene expression was measured by XR-Seq (excision repair sequencing) assay. Rhythmic expression of several core clock genes was observed in both healthy liver and tumor, with clock genes in tumor exhibiting typically robust amplitudes and a modest phase advance. Interestingly, although normal hepatic cells and hepatoma cancer cells expressed a comparable number of genes with circadian rhythmicity (clock-controlled genes), there was only about 10% overlap between the rhythmic genes in normal and cancerous cells.“Rhythmic in tumor only” genes exhibited peak expression times mainly in daytime hours, in contrast to the more common pre-dawn and pre-dusk expression times seen in healthy livers. Differential expression of genes in tumors and healthy livers across time may present an opportunity for more efficient anticancer drug treatment as a function of treatment time.  \nThe mammalian circadian clock coordinates biological functions with the environmental 24-hour light/dark cycle (1). At the molecular level, the clock is driven by a transcription– translation–degradation feedback loop consisting principally of core clock transcriptional activators and repressors (2–4). These clock proteins control their own daily rhythms of expression via interactions at E-box elements in the promoters of clock genes (5–9). Clock proteins also control the rhythmic expression of thousands of downstream circadian-controlled genes with E-box promoter elements. Physiologically, the suprachiasmatic nucleus (SCN) functions as a “central pacemaker”; the clocks in SCN cells are entrained to the light/dark  \n‡ These authors contributed equally to this work.  \n* For correspondence: Aziz Sancar, [aziz_sancar@med.unc.edu](aziz_sancar@med.unc.edu).  \ncycle mainly by photic input from the eyes; furthermore, signals from the SCN entrain the rhythms of the core clock genes/proteins in cells throughout the body (1–3, 10). Core clock proteins in cells throughout the body in turn control the rhythms of organ-specific circadian controlled genes. Synchrony in peak and trough core clock gene expression times between the SCN and organs is not perfect; notably, feeding time may also serve as an entrainment cue, causing circadian phase advances or delays in organs such as the liver, depending upon the feeding schedule (11–13).  \nNeoplasms by definition exhibit autonomy from host organs to varying degrees (14, 15). The maintenance of circadian rhythms in tumors or the lack thereof is an interesting topic with respect to cancer biology, and to the possible use of chronotherapy in the treatment of cancer, that is, the employment o","cbCairMtKIjPbMNq","https://ap.wps.com/l/cbCairMtKIjPbMNq","pdf",3295036,"English","# Introduction\n## Molecular basis of circadian clocks\n## Circadian rhythm in cancer and chronotherapy rationale\n# Methods\n## Mouse liver cancer model and cisplatin dosing schedule\n## Genome-wide measurement using XR-seq\n# Results\n## Rhythmic clock gene expression in healthy liver and tumors\n## Overlap and phase differences in rhythmic genes\n# Implications\n## Potential for time-dependent anticancer treatment","[{\"question\":\"How is circadian rhythmicity regulated at the cellular level in this study?\",\"answer\":\"It is controlled by a molecular clock involving core clock genes/proteins that operate through a transcription–translation–degradation feedback loop, generating daily rhythms and regulating downstream circadian-controlled genes.\"},{\"question\":\"How did the researchers measure gene expression rhythms in tumor and control mice?\",\"answer\":\"Mice received cisplatin every 2 hours over a 24-hour cycle, then were sacrificed 2 hours after each injection; gene expression was assessed genome-wide using the XR-seq assay.\"},{\"question\":\"What key differences in circadian rhythmic genes were found between healthy liver and tumors?\",\"answer\":\"Clock genes show robust rhythmic amplitudes in tumors with a modest phase advance, yet only about 10% overlap exists between rhythmic genes in normal and cancerous cells, and tumor-only rhythmic genes peak mainly in daytime hours.\"}]","Preservation of circadian rhythm in hepatocellular cancer | PDF",1790229473,25]