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This study identifies a pro-proliferative function of NOL3 in bladder cancer (BLCA). NOL3 reduction suppresses cell proliferation and induces stable cell-cycle arrest in two BLCA cell lines. Mechanistically, NOL3 decrease markedly inhibits PI3K/Akt signaling; the PI3K inhibitor LY294002 rescues PI3K/Akt activation and the proliferation phenotype driven by NOL3 overexpression. These findings support NOL3 as a potential therapeutic target for BLCA.",{"@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/nucleolar-protein-3-promotes-proliferation-of-bladder-cancer-cells-through-the-pi3k-akt-pathway/331574/",{"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/nucleolar-protein-3-promotes-proliferation-of-bladder-cancer-cells-through-the-pi3k-akt-pathway/331574.png","ImageObject",300,407,{"name":92,"@type":93},"Evangeline","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","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},"What role does NOL3 play in bladder cancer cell proliferation?","Question",{"text":112,"@type":113},"The study shows that NOL3 promotes proliferation of bladder cancer (BLCA) cells. Reducing NOL3 significantly inhibits proliferation and induces cell-cycle arrest in BLCA cell lines.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does NOL3 influence the PI3K/Akt pathway?",{"text":117,"@type":113},"Mechanistic evidence indicates that the PI3K/Akt pathway is considerably inhibited when NOL3 decreases in BLCA cell lines. LY294002, a PI3K inhibitor, can rescue NOL3 overexpression-mediated activation of the PI3K/Akt axis.",{"name":119,"@type":110,"acceptedAnswer":120},"Why is NOL3 suggested as a potential therapeutic target?",{"text":121,"@type":113},"Because NOL3 is upregulated in BLCA cells and its modulation affects PI3K/Akt signaling and proliferation outcomes. The results imply that targeting NOL3 may help control BLCA growth.","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},331574,1790585424,{"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":44,"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,"preview_page_count":4},13056703019662,"https://ap-avatar.wpscdn.com/avatar/be000253a8e92610077?_k=1778726343310543188","Wu et al. World Journal of Surgical Oncology (2024) 22:316  \n[https://doi.org/10.1186/s12957-024-03600-5](https://doi.org/10.1186/s12957-024-03600-5)  \nWorld Journal of Surgical Oncology  \nRESEARCH Open Access  \nNucleolar protein 3 promotes proliferation of bladder cancer cells through the PI3K-Akt pathway  \nLinfeng Wu 1, Kunyao Zhu 1, Yan Sun 1, Tinghao Li 1, Junlong Zhu 1, Hang Tong 1, Xiaoyu Zhang 1, Junrui Chen 1, Hubin Yin 1 and Weiyang He 1*  \nAbstract  \nNucleolar protein 3 (NOL3), as a markedly increased protein across a range of tumors, has been well acknowledged that plays an anti-apoptotic role in malignancies, while some novel impacts of NOL3 on metastasis and chemoresistance are demonstrated recently. In this study, we uncover another role of NOL3 on promoting proliferation in bladder cancer (BLCA) . The reduction of NOL3 significantly inhibited cell proliferation, and we detected the stable cell cycle arrest after knockdown of NOL3 in two-type BLCA cell lines. Mechanistically, we present the first evidence that the PI3K/Akt pathway was considerably inhibited with the decrease of NOL3 in BLCA cell lines. In addition, LY294002, a PI3K inhibitor, rescued NOL3 overexpression-mediated activation of the PI3K/Akt axis and the depression of proliferation in BLCA cell lines. In conclusion, our study suggests that NOL3 is upregulated in BLCA cells and promotes proliferation via the PI3K/Akt pathway, indicating that NOL3 may be a potential therapeutic target for BLCA.  \nKeywords Bladder cancer, NOL3, Cell proliferation  \nIntroduction  \nBladder cancer (BLCA) is a common malignant tumor of the urinary system, ranks as the sixth most common cancer among men and the fourth leading cause of cancer-related deaths. In recent years, both its incidence and mortality rates have shown an increasing trend [1, 2]. BLCA can be classified into non-muscleinvasive BLCA (NMIBC) and muscle-invasive BLCA (MIBC), with approximately 75% of patients diagnosed with NMIBC. However, MIBC, although less prevalent, poses a greater malignant potential and a higher threat  \n*Correspondence:  \nWeiyang He  \n[weiyang1262020@126.com](weiyang1262020@126.com)  \n1Department of Urology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing 400016, P. R. China  \nto patient survival. Even with progress in surgical techniques and pharmacological treatments, a considerable number of individuals with BLCA continue to fall victim to the illness [3]. Exploring effective therapeutic targets for BLCA can mitigate the mortality risk associated with this condition.  \nNucleolar protein 3 (NOL3) is located on human chromosome 16 and encodes a unique protein known as apoptosis repressor with caspase recruitment domain [4]. This protein was first discovered by screening for Caspase-9’s caspase recruitment domain homologous protein [4] and protects cells from apoptosis induced by multiple stimuli such as hypoxia [5], hydrogen peroxide [6], and Fas ligands [7].However, role of NOL3 in cell proliferation remain poorly understood. For instance, in pulmonary arterial hypertension, NOL3 enhances growth factor-induced cell proliferation [8]. Furthermore, NOL3  \n© The Author(s) 2024. 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 lic","cbCaibWb4p6FR2Yc","https://ap.wps.com/l/cbCaibWb4p6FR2Yc","pdf",1973598,"English","# Abstract\n# Introduction\n# Method\n## Cell lines and culture\n## Bladder cancer patients and clinical specimens","[{\"question\":\"What role does NOL3 play in bladder cancer cell proliferation?\",\"answer\":\"The study shows that NOL3 promotes proliferation of bladder cancer (BLCA) cells. Reducing NOL3 significantly inhibits proliferation and induces cell-cycle arrest in BLCA cell lines.\"},{\"question\":\"How does NOL3 influence the PI3K/Akt pathway?\",\"answer\":\"Mechanistic evidence indicates that the PI3K/Akt pathway is considerably inhibited when NOL3 decreases in BLCA cell lines. LY294002, a PI3K inhibitor, can rescue NOL3 overexpression-mediated activation of the PI3K/Akt axis.\"},{\"question\":\"Why is NOL3 suggested as a potential therapeutic target?\",\"answer\":\"Because NOL3 is upregulated in BLCA cells and its modulation affects PI3K/Akt signaling and proliferation outcomes. The results imply that targeting NOL3 may help control BLCA growth.\"}]","Nucleolar protein 3 promotes proliferation of bladder cancer cells through the PI3K-Akt pathway | PDF",1789994085,23]