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This study investigates a mechanism in which PVT1 regulates the fate determination of tumor-associated neutrophils via calcium signaling. Clinical correlations, multi-omics pathway mapping, and functional validation link PVT1 activity to neutrophil activation, apoptosis delay, and gastric cancer progression.",{"@graph":69,"@context":123},[70,84,106],{"@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/calcium-overload-via-pvt1-reprograms-neutrophil-fate-and-constrains-gastric-cancer-progression/371732/",{"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/calcium-overload-via-pvt1-reprograms-neutrophil-fate-and-constrains-gastric-cancer-progression/371732.png","ImageObject",300,407,{"name":92,"@type":93},"McQueen","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"How does PVT1 expression relate to neutrophil infiltration in gastric cancer tissues?","Question",{"text":113,"@type":114},"Clinical analysis of 90 gastric cancer cases shows that PVT1 expression correlates with neutrophil infiltration in tumor tissues. Higher PVT1 expression is negatively associated with neutrophil infiltration and is linked to worse prognosis in a PVT1 + CD66b subgroup.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What calcium-related changes occur after silencing PVT1 in gastric cancer cells?",{"text":118,"@type":114},"Silencing PVT1 upregulates calcium signaling pathway-related genes, including RYR2 and RYR3, accompanied by a marked increase in intracellular Ca2+ concentration.",{"name":120,"@type":111,"acceptedAnswer":121},"How does PVT1 knockdown affect neutrophils and gastric cancer progression in functional models?",{"text":122,"@type":114},"Conditioned medium from PVT1-knockdown gastric cancer cells promotes neutrophil activation, delays apoptosis, and amplifies intracellular Ca2+ signaling. It also suppresses gastric cancer cell proliferation, migration, and invasion, with xenograft tumors showing reduced volume and lower Ki67.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},371732,1790792881,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},5909890329169,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","Wang et al. Journal of Translational Medicine (2025) 23:878  \n[https://doi.org/10.1186/s12967-025-06912-6](https://doi.org/10.1186/s12967-025-06912-6)  \nJournal of Translational Medicine  \nRESEARCH Open Access  \nCalcium overload via PVT1 reprograms  neutrophil fate and constrains gastric cancer progression  \nDong Wang 1†, Yunlong Li2†, Xiaoyu Peng 1, Lulu Zhang 1, Ying Zhang3, Xue Guan4, Xiao Liang3, Songbin Fu3 and Jingcui Yu 1,3*  \nAbstract  \nBackground The aberrant upregulation of PVT1 in gastric cancer (GC) has emerged as a critical molecular marker, while its mechanism of remodeling the tumor microenvironment (TME) through metabolic regulation remains unclear. This study aims to unveil the novel mechanism by which PVT1 regulates the fate determination of tumorassociated neutrophils (TANs) via the calcium signaling pathway.  \nMethods Clinical analysis of 90 GC cases revealed a correlation between PVT1 expression and neutrophil infiltration in tumor tissues. Mechanistically, multi-omics integration of transcriptomics and 4D-label-free quantitative proteomics identified PVT1-associated pathways driving GC progression. Functional validation through in vitro and in vivo models demonstrated PVT1’s oncogenic role, while transcriptomic profiling further decoded neutrophil activation mechanisms regulated by PVT1 .  \nResults The expression of PVT1 was significantly elevated in GC tissues compared to adjacent non-tumor tissues (p \u003C 0. 001), with 73. 3% of cases showing an increased proportion of PVT1-positive cells. High PVT1 expression negatively correlated with the infiltration of neutrophils (r = − 0 . 3554, p = 0 . 0012), and patients in the PVT1 + CD66bsubgroup exhibited the poorest prognosis, characterized by a median survival of 20.5 months and a mortality  \nrate of 72 . 5% . Silencing PVT1 upregulated calcium signaling pathway-related genes (RYR2 and RYR3) in GC cells, accompanied by a marked increase in intracellular Ca2⁺ concentration (p \u003C 0. 01) . Proteomic analysis revealed that PVT1 knockdown significantly enhanced the secretion of synaptopodin (SYNPO), which demonstrated co-expression and physical interactions with calcium channel proteins RYR2/RYR3 . PVT1 knockdown markedly suppressed GC  \ncell proliferation, migration, and invasion (p \u003C 0. 05) while elevating the expression of γ-H2AX (p \u003C 0. 05) . In xenograft models, tumors with PVT1 knockdown displayed reduced volume and decreased Ki67 expression (p \u003C 0. 01) . Conditioned medium from PVT1-knockdown GC cells promoted neutrophil activation, delayed apoptosis, and amplified intracellular Ca2⁺ signaling. Exogenous SYNPO supplementation mimicked these effects and attenuated neutrophil replicative senescence by modulating p53 pathway-associated genes (TP53, CHEK1, and SERPINE1) .  \n†Dong Wang andYunlong Li have contributed equally to this work.  \n*Correspondence:  \nJingcui Yu[yujingcui@ems.hrbmu.edu.cn](yujingcui@ems.hrbmu.edu.cn)  \nFull list of author information is available at the end of the article  \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 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 licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licenc","cbCaiqSSt6ViaFGy","https://ap.wps.com/l/cbCaiqSSt6ViaFGy","pdf",6561534,18,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions","[{\"question\":\"How does PVT1 expression relate to neutrophil infiltration in gastric cancer tissues?\",\"answer\":\"Clinical analysis of 90 gastric cancer cases shows that PVT1 expression correlates with neutrophil infiltration in tumor tissues. Higher PVT1 expression is negatively associated with neutrophil infiltration and is linked to worse prognosis in a PVT1 + CD66b subgroup.\"},{\"question\":\"What calcium-related changes occur after silencing PVT1 in gastric cancer cells?\",\"answer\":\"Silencing PVT1 upregulates calcium signaling pathway-related genes, including RYR2 and RYR3, accompanied by a marked increase in intracellular Ca2+ concentration.\"},{\"question\":\"How does PVT1 knockdown affect neutrophils and gastric cancer progression in functional models?\",\"answer\":\"Conditioned medium from PVT1-knockdown gastric cancer cells promotes neutrophil activation, delays apoptosis, and amplifies intracellular Ca2+ signaling. It also suppresses gastric cancer cell proliferation, migration, and invasion, with xenograft tumors showing reduced volume and lower Ki67.\"}]","Calcium overload via PVT1 reprograms neutrophil fate and constrains gastric cancer progression | PDF",1790192726,45]