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The letter summarizes evidence that HOXC6 is upregulated at mRNA and protein levels in cancerous tissues, and that HOXC6 silencing suppresses BLCA cell proliferation, migration, invasion, promotes apoptosis, and causes G0/G1 cell-cycle arrest. It also describes HOXC6’s regulation of chemical carcinogenesis and reactive oxygen species–related pathways, strongly linked to TIMELESS via promoter binding. The work positions the HOXC6-TIMELESS axis as a potential biomarker and therapeutic target to advance BLCA research and treatment.",{"@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/hoxc6-timeless-axis-unveiling-novel-therapeutic-strategies-in-bladder-cancer/369718/",{"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/hoxc6-timeless-axis-unveiling-novel-therapeutic-strategies-in-bladder-cancer/369718.png","ImageObject",300,407,{"name":92,"@type":93},"Stanley","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-24","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does HOXC6 play in bladder cancer according to the letter?","Question",{"text":112,"@type":113},"HOXC6 is reported to be elevated in BLCA tissues, and silencing HOXC6 inhibits proliferation, migration, and invasion while inducing apoptosis and arresting cells in G0/G1.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How is TIMELESS connected to the HOXC6 mechanism?",{"text":117,"@type":113},"HOXC6 is described as regulating pathways related to chemical carcinogenesis and reactive oxygen species with a strong association to TIMELESS, supported by binding signals in the TIMELESS promoter region.",{"name":119,"@type":110,"acceptedAnswer":120},"Why is the HOXC6-TIMELESS axis considered important for therapy and diagnosis?",{"text":121,"@type":113},"The letter argues that the HOXC6-TIMELESS axis may serve as a promising molecular target, offering a basis for precision therapies and biomarker strategies to improve BLCA management and outcomes.","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},369718,1790245620,{"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":24,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":24,"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},2336477405376,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","| W | J | C | O | World Journal of\u003Cbr>Clinical Oncology |\n| --- | --- | --- | --- | --- |\n\nSubmit a Manuscript: [https://www.f6publishing.com](https://www.f6publishing.com) World J Clin Oncol 2025 July 24; 16(7): 108071  \nDOI: 10.5306/wjco.v16.i7.108071 ISSN 2218-4333 (online)  \nLETTER TO THE EDITOR  \nHOXC6-TIMELESS axis: Unveiling novel therapeutic strategies in bladder cancer  \nMeng-Meng Shi, Ming-Yue Guan, Shi Li, Jie-Yu Guo, Xing-Zhen Chen, Jing-Feng Tang, Ce-Fan Zhou  \nSpecialty type: Oncology  \nProvenance and peer review:  \nInvited article; Externally peer reviewed.  \nPeer-review model: Single blind  \nPeer-review report’s classification Scientific Quality: Grade B  \nNovelty: Grade B  \nCreativity or Innovation: Grade B  \nScientific Significance: Grade B  \nP-Reviewer: Oviedo RJ  \nReceived: April 8, 2025  \nRevised: April 27, 2025  \nAccepted: June 11, 2025  \nPublished online: July 24, 2025  \nProcessing time: 109 Days and 6.2 Hours  \nMeng-Meng Shi, Ming-Yue Guan, Shi Li, Jie-Yu Guo, Jing-Feng Tang, Ce-Fan Zhou, School of Life and Health Sciences, Institute of Biomedical Research, National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, Hubei Province, China  \nXing-Zhen Chen, Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton T6G 2H7, Canada  \nCorresponding author: Ce-Fan Zhou, PhD, Professor, School of Life and Health Sciences, Institute of Biomedical Research, National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, No. 28 Nanli Road, Wuhan 430068, Hubei Province, China.  \n[cefan@hbut.edu.cn](cefan@hbut.edu.cn)  \nAbstract  \nBladder cancer (BLCA) is a highly invasive malignancy with limited targeted therapies. Lu et al reveal the oncogenic role of HOXC6 in BLCA by showing its elevated mRNA and protein levels in cancerous tissues. Silencing HOXC6 significantly inhibits BLCA cell proliferation, migration and invasion, induces apoptosis and arrests the cell cycle at G0/G1 . In addition, HOXC6 also regulates pathways related to chemical carcinogenesis and reactive oxygen species, with a strong association with the target gene TIMELESS, supported by binding signals in its promoter region. Here, we discuss the role of HOXC6 as a potential biomarker and therapeutic target, contributing to a deeper understanding of the HOXC6-TIMELESS axis and its implications for advancing BLCA research and therapy.  \nKey Words: Bladder cancer; HOXC6; Gene regulation; TIMELESS; Targeted therapy; Molecular oncology  \n©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.  \n WJCO  [https://www.wjgnet.com](https://www.wjgnet.com) 1 July 24, 2025  Volume 16  Issue 7   \nShi MM et al. HOXC6-TIMELESS axis in BLCA therapy  \nCore Tip: The significant correlation between HOXC6 overexpression and bladder cancer (BLCA) progression has led to the establishment of a novel HOXC6-TIMELESS regulatory axis. In this letter, we aim to highlight the HOXC6-TIMELESS axis as a promising molecular target for the diagnosis and treatment of BLCA. Additionally, exploring therapeutic strategies such as RNA-based interventions, or circadian rhythm modulation may offer promising avenues to improve BLCA management and patient prognosis.  \nCitation: Shi MM, Guan MY, Li S, Guo JY, Chen XZ, Tang JF, Zhou CF. HOXC6-TIMELESS axis: Unveiling novel therapeutic strategies in bladder cancer. World J Clin Oncol 2025; 16(7): 108071  \nURL: [https://www.wjgnet.com/2218-4333/full/v16/i7/108071.htm](https://www.wjgnet.com/2218-4333/full/v16/i7/108071.htm)  \nDOI: [https://dx.doi.org/10.5306/wjco.v16.i7.108071](https://dx.doi.org/10.5306/wjco.v16.i7.108071)  \nBladder cancer (BLCA) is a common malignancy of the urinary tract, with an estimated 613000 new cases and 220000 deaths wo","cbCailwjwhAjZKpG","https://ap.wps.com/l/cbCailwjwhAjZKpG","pdf",705732,"English","# Core Tip\n## HOXC6-TIMELESS regulatory axis as a molecular target\n# Abstract\n## HOXC6 role in BLCA progression\n## Mechanistic link to TIMELESS via promoter binding\n## Therapeutic and biomarker implications","[{\"question\":\"What role does HOXC6 play in bladder cancer according to the letter?\",\"answer\":\"HOXC6 is reported to be elevated in BLCA tissues, and silencing HOXC6 inhibits proliferation, migration, and invasion while inducing apoptosis and arresting cells in G0/G1.\"},{\"question\":\"How is TIMELESS connected to the HOXC6 mechanism?\",\"answer\":\"HOXC6 is described as regulating pathways related to chemical carcinogenesis and reactive oxygen species with a strong association to TIMELESS, supported by binding signals in the TIMELESS promoter region.\"},{\"question\":\"Why is the HOXC6-TIMELESS axis considered important for therapy and diagnosis?\",\"answer\":\"The letter argues that the HOXC6-TIMELESS axis may serve as a promising molecular target, offering a basis for precision therapies and biomarker strategies to improve BLCA management and outcomes.\"}]","HOXC6-TIMELESS axis: Unveiling novel therapeutic strategies in bladder cancer | PDF",1790184201,13]