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Bioinformatics assessed CHD1L expression and prognostic relevance, while in vitro assays measured proliferation, cell-cycle changes, apoptosis, and migration/invasion. In vivo efficacy was tested using a nude mouse xenograft model. Mechanistically, CHD1L inhibition activated FOXO3 and its downstream target PUMA to drive apoptosis, with FOXO3 suppression reversing OTI-611 effects. OTI-611 also synergized with docetaxel to enhance cell death and counter docetaxel resistance.",{"@graph":69,"@context":126},[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/targeting-chd1l-suppresses-prostate-cancer-progression-via-the-foxo3-puma-axis/457538/",{"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/targeting-chd1l-suppresses-prostate-cancer-progression-via-the-foxo3-puma-axis/457538.png","ImageObject",300,407,{"name":92,"@type":93},"Mary Man","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-22","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":19},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118,122],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main focus of the study?","Question",{"text":112,"@type":113},"The study examines how targeting CHD1L affects prostate cancer progression and evaluates the therapeutic potential of the CHD1L inhibitor OTI-611.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was CHD1L involvement tested in prostate cancer?",{"text":117,"@type":113},"CHD1L expression and prognostic significance were assessed using bioinformatics, and functional effects were measured with assays for proliferation, apoptosis, and migration/invasion, plus an in vivo xenograft model.",{"name":119,"@type":110,"acceptedAnswer":120},"What mechanism explains OTI-611’s anti-tumor effects?",{"text":121,"@type":113},"CHD1L inhibition induces FOXO3 expression and its downstream target PUMA, promoting apoptosis; suppressing FOXO3 reverses OTI-611-induced apoptosis.",{"name":123,"@type":110,"acceptedAnswer":124},"Does OTI-611 work better with existing chemotherapy?",{"text":125,"@type":113},"Yes. 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Journal of Translational Medicine (2026) 24:41  \n[https://doi.org/10.1186/s12967-025-07529-5](https://doi.org/10.1186/s12967-025-07529-5)  \nJournal of Translational Medicine  \nRESEARCH Open Access  \nTargeting CHD1L suppresses prostate cancer progression via the FOXO3-PUMA axis  \nPusheng Hui 1, Yanru Lai2, Haiqi Fan2, Qinrong Yan2, Yue Yang3, Zhe Chen2*, Yu Hou2* and Youlin Kuang 1*  \nAbstract  \nBackground Prostate cancer (PCa) is one of the most common malignancies in men worldwide, and advanced or metastatic disease remains a major therapeutic challenge. Chromodomain helicase DNA binding protein  \n1-like (CHD1L) has been implicated as an oncogenic driver in multiple cancer types, yet its role in prostate cancer pathogenesis is not fully defined. The purpose of this study is to investigate the biological significance of CHD1L in prostate cancer and to evaluate the therapeutic potential of its selective inhibitor OTI-611 .  \nMethods Bioinformatics analyses were conducted to assess the expression, prognostic significance of CHD1L in PCa patients. In vitro, cell viability, cycle progression, apoptosis, and migration/invasion were evaluated using CCK-8, colony formation, flow cytometry, transwell assays. In vivo treatment potential of OTI-611 was assessed through a nude mouse xenograft model. Protein and mRNA levels were determined by western blot and qPCR, respectively. Synergism of OTI-611 and docetaxel was determined using SynergyFinder 3.0.  \nResults We demonstrated that CHD1L was significantly upregulated in PCa patients and correlates with poor prognosis. Genetic knockdown of CHD1L substantially inhibits PCa cell proliferation and induces apoptosis. Moreover, inhibition of CHD1L by the small molecule OTI-611 significantly suppresses PCa cell proliferation, migration, and invasion, and induces apoptosis both in vitro and in vivo. Mechanistically, inhibition of CHD1L induces the expression of FOXO3 (a classic transcription factor) and its downstream target PUMA (a key apoptosis inducer) . Restricting the expression of FOXO3 significantly reverses the anti-tumor effects induced by OTI-611 . Furthermore, OTI-611 synergizes with docetaxel to enhance apoptotic cell death, providing a promising strategy to overcome docetaxel resistance. Conclusions Our study demonstrates that CHD1L is markedly upregulated in prostate cancer and contributes to tumor progression. Pharmacological inhibition of CHD1L with the selective inhibitor OTI-611 significantly suppresses proliferation, migration, and invasion, while inducing apoptosis in vitro and in vivo. Mechanistically, these effects are mediated through activation of the FOXO3–PUMA axis, as FOXO3 suppression abrogates OTI-611–induced apoptosis. Moreover, OTI-611 exhibits strong synergy with docetaxel, enhancing apoptotic cell death and providing a potential strategy to improve therapeutic efficacy in prostate cancer.  \nKeywords Prostate cancer, CHD1L, FOXO3, PUMA, Docetaxel  \n*Correspondence: Zhe Chen[chenzhe925@cqmu.edu.cn](chenzhe925@cqmu.edu.cn)[ ](chenzhe925@cqmu.edu.cn)Yu Hou [houyu@cqmu.edu.cn](houyu@cqmu.edu.cn)[ ](houyu@cqmu.edu.cn)Youlin Kuang  \n[203412@hospital.cqmu.edu.cn](203412@hospital.cqmu.edu.cn)  \n1Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China  \n2School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China  \n3Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China  \n© The Author(s) 2025. 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 th","cbCaibd3kf8J7LvS","https://ap.wps.com/l/cbCaibd3kf8J7LvS","pdf",11185638,"English","# Background\n## Role of CHD1L and therapeutic challenge\n# Methods\n## Bioinformatics and experimental assays\n## In vivo xenograft and molecular analyses\n# Results\n## CHD1L upregulation and functional inhibition\n## FOXO3-PUMA axis mechanism\n## Synergy with docetaxel\n# Conclusions","[{\"question\":\"What is the main focus of the study?\",\"answer\":\"The study examines how targeting CHD1L affects prostate cancer progression and evaluates the therapeutic potential of the CHD1L inhibitor OTI-611.\"},{\"question\":\"How was CHD1L involvement tested in prostate cancer?\",\"answer\":\"CHD1L expression and prognostic significance were assessed using bioinformatics, and functional effects were measured with assays for proliferation, apoptosis, and migration/invasion, plus an in vivo xenograft model.\"},{\"question\":\"What mechanism explains OTI-611’s anti-tumor effects?\",\"answer\":\"CHD1L inhibition induces FOXO3 expression and its downstream target PUMA, promoting apoptosis; suppressing FOXO3 reverses OTI-611-induced apoptosis.\"},{\"question\":\"Does OTI-611 work better with existing chemotherapy?\",\"answer\":\"Yes. OTI-611 synergizes with docetaxel, enhancing apoptotic cell death and helping to address docetaxel resistance.\"}]","Targeting CHD1L suppresses prostate cancer progression via the FOXO3-PUMA axis | PDF",1790749655,48]