Targeting neuropilin-1 and neutralizing interleukin-6 inhibits cancer stem cell formation in bladder cancer cells

Targeting neuropilin-1 and neutralizing interleukin-6 inhibits cancer stem cell formation in bladder cancer cells | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Targeting neuropilin-1 and neutralizing interleukin-6 inhibits cancer stem cell formation in bladder cancer cells Hsiao-Wen Weng, Hui-Kung Ting, Hsiao-Hsien Wang, Ta-Jung Peng, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8052232/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Mar, 2026 Read the published version in Journal of Translational Medicine → Version 1 posted 4 You are reading this latest preprint version Abstract Background Bladder urothelial carcinoma (BLCA) recurrence is frequently driven by an aggressive tumor microenvironment and the persistence of cancer stem cells (CSCs), both of which contribute to therapeutic resistance and metastasis. Neuropilin-1 (NRP1) is increasingly recognized as a key orchestrator of epithelial-mesenchymal transition (EMT), endowing tumor cells with enhanced chemoresistance, metastatic potential, and stemness. However, the precise mechanisms by which NRP1 exacerbates BLCA aggressiveness remain unclear. Methods Gene expression in BLCA patients was analyzed via the TCGA dataset. In vitro studies utilized genetic modulation of NRP1 to dissect its role in BLCA progression. Functional assays were used to assess the impact of NRP1 on proliferation, migration, invasion, and stemness. Bulk RNA-sequencing was used to investigate transcriptomic consequences of NRP1 modulation. The role of NRP1 in regulating interleukin-6 (IL-6) was examined using RT-qPCR, ELISA, and immunohistochemistry. A subcutaneous nude mouse model using T24 CSCs was used to validate in vivo therapeutic strategies. Results High NRP1 expression was significantly associated with tumor drug resistance, stemness, EMT features, and poor overall survival in BLCA patients. Genetic ablation of NRP1 markedly suppressed BLCA cell proliferation, migration, invasion, and CSC properties. Mechanistically, NRP1 depletion profoundly reduced IL-6 secretion, leading to a downstream decrease in p-STAT3 activity. Importantly, exogenous IL-6 rescued stemness traits in NRP1-deficient CSCs, establishing IL-6 as a critical effector of the protumorigenic functions of NRP1. A novel combinatorial therapeutic strategy in which the NRP1 inhibitor EG00229 was coadministered with the neutralizing IL-6 antibody siltuximab significantly attenuated spheroid invasion in vitro and abrogated CSC maintenance both in vitro and in vivo. Conclusions The NRP1-IL-6-STAT3 signaling axis promotes CSC maintenance and aggressive tumor phenotypes in BLCA. This study identifies a promising dual-targeting strategy against NRP1 and IL-6 with significant translational potential for improving outcomes in BLCA patients. Keywords Bladder urothelial carcinoma, Epithelial-mesenchymal transition, Cancer stem cells, Interleukin-6, Neuropilin-1, Tumor microenvironment Bladder urothelial carcinoma Epithelial-mesenchymal transition Cancer stem cells Interleukin-6 Neuropilin-1 Tumor microenvironment Full Text Supplementary Files Supplementarymaterial1.docx Supplementarymaterial2.docx SupplementaryFig1.pdf SupplementaryFig2.pdf SupplementaryFig3.pdf SupplementaryFig4.pdf SupplementaryFig5.pdf SupplementaryFig6.pdf SupplementaryFig7.pdf Cite Share Download PDF Status: Published Journal Publication published 04 Mar, 2026 Read the published version in Journal of Translational Medicine → Version 1 posted Reviewers agreed at journal 14 Nov, 2025 Reviewers invited by journal 12 Nov, 2025 Editor assigned by journal 08 Nov, 2025 First submitted to journal 06 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8052232","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":543891818,"identity":"d87184fa-b008-494e-8ec8-09cc3ddb7ec6","order_by":0,"name":"Hsiao-Wen Weng","email":"","orcid":"","institution":"National Defense Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hsiao-Wen","middleName":"","lastName":"Weng","suffix":""},{"id":543891819,"identity":"d385f672-edb9-4842-81a2-96947def8f8c","order_by":1,"name":"Hui-Kung Ting","email":"","orcid":"","institution":"National Defense Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hui-Kung","middleName":"","lastName":"Ting","suffix":""},{"id":543891820,"identity":"f4112d49-f90c-4e7a-aedf-57bab8e7f4ed","order_by":2,"name":"Hsiao-Hsien Wang","email":"","orcid":"","institution":"Cheng Hsin General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hsiao-Hsien","middleName":"","lastName":"Wang","suffix":""},{"id":543891821,"identity":"8e7ac518-9739-44c1-b2e4-344ab8d09f10","order_by":3,"name":"Ta-Jung Peng","email":"","orcid":"","institution":"National Yang Ming Chiao Tung University","correspondingAuthor":false,"prefix":"","firstName":"Ta-Jung","middleName":"","lastName":"Peng","suffix":""},{"id":543891822,"identity":"d2e1e0ca-4cab-4c55-b107-dddcf189e373","order_by":4,"name":"Shye-Jye Tang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2klEQVRIiWNgGAWjYHCCxAcMDBIyMB5jAyH1PAwMyQZALUCaGaaFmaAWNgkITawWe/4Dz6pu1FjwMEj3H3zMw2Aju+EA/zEJvLZIJKTdzjkGdJjMYWZjHoY04w0HmNkIaGEAamEDapFIZpPmYTicCNJyA68W/gNpxTn/4Fr+E6GFISGNObcNruUAEVpuJCRL5/ZJ8LBJJBsbzjFINp55mNn8Bz4t7P1nEj/nfKuT45dIfPjgTYWdbN/xxscG+LQA7UkAU2xgEqSWQLSA7DlAUMkoGAWjYBSMcAAARvc7+ufH8ZkAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-4828-7456","institution":"National Taiwan Ocean University","correspondingAuthor":true,"prefix":"","firstName":"Shye-Jye","middleName":"","lastName":"Tang","suffix":""},{"id":543891823,"identity":"df40487f-fc10-48e0-a17d-33ff6accbfc4","order_by":5,"name":"Kuang-Hui Sun","email":"","orcid":"","institution":"National Yang Ming Chiao Tung University","correspondingAuthor":false,"prefix":"","firstName":"Kuang-Hui","middleName":"","lastName":"Sun","suffix":""}],"badges":[],"createdAt":"2025-11-07 02:30:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8052232/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8052232/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12967-026-07943-3","type":"published","date":"2026-03-04T16:00:05+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":96610820,"identity":"edba6c34-c6c7-4235-9862-3c768e9f7f34","added_by":"auto","created_at":"2025-11-24 09:32:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1385691,"visible":true,"origin":"","legend":"","description":"","filename":"Figure1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8052232/v1/6815e725ec467767354100df.pdf"},{"id":96611065,"identity":"32efb921-1488-4d1d-8bbd-ceee457911df","added_by":"auto","created_at":"2025-11-24 09:32:30","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":271083,"visible":true,"origin":"","legend":"","description":"","filename":"Figure2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8052232/v1/e93b32158e54d5202a43de07.pdf"},{"id":96610917,"identity":"136dcb23-75e1-4ab7-8473-9a40c3ffcce0","added_by":"auto","created_at":"2025-11-24 09:32:12","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":145817,"visible":true,"origin":"","legend":"","description":"","filename":"Figure3.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8052232/v1/5fe99b07030375c91bffb3b6.pdf"},{"id":96610672,"identity":"0df156b8-efa8-4c13-b3b6-371b43f4443f","added_by":"auto","created_at":"2025-11-24 09:32:02","extension":"pdf","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":296559,"visible":true,"origin":"","legend":"","description":"","filename":"Figure4.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8052232/v1/6bddeca81dd49479647cab95.pdf"},{"id":96610620,"identity":"04d259d8-25c0-467a-8ce3-adcd36801669","added_by":"auto","created_at":"2025-11-24 09:32:01","extension":"pdf","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":171293,"visible":true,"origin":"","legend":"","description":"","filename":"Figure5.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8052232/v1/fcbd14ca2fcb333abc97205a.pdf"},{"id":96610818,"identity":"d25abaca-aceb-4448-b7a1-05648decfd94","added_by":"auto","created_at":"2025-11-24 09:32:06","extension":"pdf","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":242373,"visible":true,"origin":"","legend":"","description":"","filename":"Figure6.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8052232/v1/6d72be6501b09d321b854644.pdf"},{"id":96610863,"identity":"021ab0c7-d965-4b06-9d32-085874ff1124","added_by":"auto","created_at":"2025-11-24 09:32:08","extension":"pdf","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":610200,"visible":true,"origin":"","legend":"","description":"","filename":"Figure7.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8052232/v1/66fb70370af4c78ee886a841.pdf"},{"id":96610813,"identity":"f8dcc26d-8467-4e99-b14f-90831f7c88cf","added_by":"auto","created_at":"2025-11-24 09:32:06","extension":"pdf","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":576268,"visible":true,"origin":"","legend":"","description":"","filename":"Figure8.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8052232/v1/0ca23defb81aa8b507a86aa3.pdf"},{"id":96610866,"identity":"3033d73e-de3b-4565-8483-da4cf09301e7","added_by":"auto","created_at":"2025-11-24 09:32:08","extension":"xml","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":14833,"visible":true,"origin":"","legend":"","description":"","filename":"jtrmJTRMD2519678.xml","url":"https://assets-eu.researchsquare.com/files/rs-8052232/v1/4e1dae406513bdbb915772c0.xml"},{"id":96610903,"identity":"ecad5c50-3218-43f5-9fc5-7b73532aab7b","added_by":"auto","created_at":"2025-11-24 09:32:11","extension":"xml","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1624,"visible":true,"origin":"","legend":"","description":"","filename":"JTRMD2519678154178.go.xml","url":"https://assets-eu.researchsquare.com/files/rs-8052232/v1/637053e9713abde0edc5d334.xml"},{"id":96611086,"identity":"24168e1c-1868-4315-a7cd-6b1809eee271","added_by":"auto","created_at":"2025-11-24 09:32:32","extension":"xml","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":837,"visible":true,"origin":"","legend":"","description":"","filename":"JTRMD2519678Import.xml","url":"https://assets-eu.researchsquare.com/files/rs-8052232/v1/6ee32cf539081b336dc3d570.xml"},{"id":104252203,"identity":"0a65c21d-397c-4864-954b-3cb7d55bb365","added_by":"auto","created_at":"2026-03-09 16:17:37","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1888760,"visible":true,"origin":"","legend":"","description":"","filename":"JTM20251029W.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8052232/v1_covered_623154c8-09f8-4bab-b7a2-93fec4be218e.pdf"},{"id":96610915,"identity":"9a5cac90-5436-41a3-8169-cbb209227376","added_by":"auto","created_at":"2025-11-24 09:32:12","extension":"docx","order_by":12,"title":"","display":"","copyAsset":false,"role":"supplement","size":26246883,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8052232/v1/cba51b92ffba1af357dfee71.docx"},{"id":96610880,"identity":"b06b1bee-3a39-4d0a-8b14-5bf728015942","added_by":"auto","created_at":"2025-11-24 09:32:09","extension":"docx","order_by":13,"title":"","display":"","copyAsset":false,"role":"supplement","size":48602,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial2.docx","url":"https://assets-eu.researchsquare.com/files/rs-8052232/v1/fa509f58d2770b33d4c38756.docx"},{"id":96610832,"identity":"2f18360d-38ab-4cab-8a7d-4060e46211b1","added_by":"auto","created_at":"2025-11-24 09:32:07","extension":"pdf","order_by":14,"title":"","display":"","copyAsset":false,"role":"supplement","size":362876,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFig1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8052232/v1/00c816b7fea5f2d80bab4305.pdf"},{"id":96610812,"identity":"86d81b60-dd86-4139-9e6e-934c7ea5dd08","added_by":"auto","created_at":"2025-11-24 09:32:06","extension":"pdf","order_by":15,"title":"","display":"","copyAsset":false,"role":"supplement","size":212927,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFig2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8052232/v1/aba5418c6bcd2735be8eeab8.pdf"},{"id":96611055,"identity":"d0a0625a-484e-449b-a3b1-e67899612c5a","added_by":"auto","created_at":"2025-11-24 09:32:26","extension":"pdf","order_by":16,"title":"","display":"","copyAsset":false,"role":"supplement","size":172230,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFig3.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8052232/v1/f4e276fff3a51315bb263cfd.pdf"},{"id":96611019,"identity":"9eca24d1-040b-419f-8b60-679361739489","added_by":"auto","created_at":"2025-11-24 09:32:19","extension":"pdf","order_by":17,"title":"","display":"","copyAsset":false,"role":"supplement","size":203856,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFig4.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8052232/v1/773269cab039a6810cbf981a.pdf"},{"id":96610949,"identity":"84f96624-5486-40eb-b652-ba30daa7e21c","added_by":"auto","created_at":"2025-11-24 09:32:16","extension":"pdf","order_by":18,"title":"","display":"","copyAsset":false,"role":"supplement","size":166181,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFig5.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8052232/v1/d20e2920e7a133a44a37dfa2.pdf"},{"id":96610815,"identity":"88ba2b63-83fe-4073-b324-af8293345e2c","added_by":"auto","created_at":"2025-11-24 09:32:06","extension":"pdf","order_by":19,"title":"","display":"","copyAsset":false,"role":"supplement","size":109174,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFig6.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8052232/v1/76f9c73d1c978ad0d65be500.pdf"},{"id":96610805,"identity":"08c16c32-7c80-4818-8370-97e87fcf60d4","added_by":"auto","created_at":"2025-11-24 09:32:06","extension":"pdf","order_by":20,"title":"","display":"","copyAsset":false,"role":"supplement","size":380896,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFig7.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8052232/v1/8c8643e4ef74eb2779fe6b37.pdf"}],"financialInterests":"","formattedTitle":"Targeting neuropilin-1 and neutralizing interleukin-6 inhibits cancer stem cell formation in bladder cancer cells","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-translational-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jtrm","sideBox":"Learn more about [Journal of Translational Medicine](http://translational-medicine.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/jtrm/default.aspx","title":"Journal of Translational Medicine","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Bladder urothelial carcinoma, Epithelial-mesenchymal transition, Cancer stem cells, Interleukin-6, Neuropilin-1, Tumor microenvironment","lastPublishedDoi":"10.21203/rs.3.rs-8052232/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8052232/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground Bladder urothelial carcinoma (BLCA) recurrence is frequently driven by an aggressive tumor microenvironment and the persistence of cancer stem cells (CSCs), both of which contribute to therapeutic resistance and metastasis. Neuropilin-1 (NRP1) is increasingly recognized as a key orchestrator of epithelial-mesenchymal transition (EMT), endowing tumor cells with enhanced chemoresistance, metastatic potential, and stemness. However, the precise mechanisms by which NRP1 exacerbates BLCA aggressiveness remain unclear.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMethods Gene expression in BLCA patients was analyzed via the TCGA dataset. In vitro studies utilized genetic modulation of NRP1 to dissect its role in BLCA progression. Functional assays were used to assess the impact of NRP1 on proliferation, migration, invasion, and stemness. Bulk RNA-sequencing was used to investigate transcriptomic consequences of NRP1 modulation. The role of NRP1 in regulating interleukin-6 (IL-6) was examined using RT-qPCR, ELISA, and immunohistochemistry. A subcutaneous nude mouse model using T24 CSCs was used to validate in vivo therapeutic strategies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eResults High NRP1 expression was significantly associated with tumor drug resistance, stemness, EMT features, and poor overall survival in BLCA patients. Genetic ablation of NRP1 markedly suppressed BLCA cell proliferation, migration, invasion, and CSC properties. Mechanistically, NRP1 depletion profoundly reduced IL-6 secretion, leading to a downstream decrease in p-STAT3 activity. Importantly, exogenous IL-6 rescued stemness traits in NRP1-deficient CSCs, establishing IL-6 as a critical effector of the protumorigenic functions of NRP1. A novel combinatorial therapeutic strategy in which the NRP1 inhibitor EG00229 was coadministered with the neutralizing IL-6 antibody siltuximab significantly attenuated spheroid invasion in vitro and abrogated CSC maintenance both in vitro and in vivo.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConclusions The NRP1-IL-6-STAT3 signaling axis promotes CSC maintenance and aggressive tumor phenotypes in BLCA. This study identifies a promising dual-targeting strategy against NRP1 and IL-6 with significant translational potential for improving outcomes in BLCA patients. Keywords Bladder urothelial carcinoma, Epithelial-mesenchymal transition, Cancer stem cells, Interleukin-6, Neuropilin-1, Tumor microenvironment\u003c/p\u003e","manuscriptTitle":"Targeting neuropilin-1 and neutralizing interleukin-6 inhibits cancer stem cell formation in bladder cancer cells","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-24 09:25:59","doi":"10.21203/rs.3.rs-8052232/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-11-14T07:07:36+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-12T11:25:17+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-08T10:27:49+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Translational Medicine","date":"2025-11-06T21:29:19+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-translational-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jtrm","sideBox":"Learn more about [Journal of Translational Medicine](http://translational-medicine.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/jtrm/default.aspx","title":"Journal of Translational Medicine","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c2029c5d-f165-430e-bea8-93e1be747080","owner":[],"postedDate":"November 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-09T16:14:36+00:00","versionOfRecord":{"articleIdentity":"rs-8052232","link":"https://doi.org/10.1186/s12967-026-07943-3","journal":{"identity":"journal-of-translational-medicine","isVorOnly":false,"title":"Journal of Translational Medicine"},"publishedOn":"2026-03-04 16:00:05","publishedOnDateReadable":"March 4th, 2026"},"versionCreatedAt":"2025-11-24 09:25:59","video":"","vorDoi":"10.1186/s12967-026-07943-3","vorDoiUrl":"https://doi.org/10.1186/s12967-026-07943-3","workflowStages":[]},"version":"v1","identity":"rs-8052232","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8052232","identity":"rs-8052232","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}