RGS3 functions as a tumor promoter by facilitating the activation of the TGF-β signaling pathway and promoting EMT in ovarian cancer. | 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Article RGS3 functions as a tumor promoter by facilitating the activation of the TGF-β signaling pathway and promoting EMT in ovarian cancer. Jinhua Zhou, Zizhao Wang, HuaTing Sun, Shunpeng Zhu, Fang Wang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5307214/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Jun, 2025 Read the published version in Cell Death Discovery → Version 1 posted You are reading this latest preprint version Abstract Ovarian cancer (OC) is one of the most common and lethal solid malignancies among women, with its incidence steadily rising. Despite substantial advancements in OC research, its pathogenesis remains largely elusive. Recent studies indicate that the regulator of G protein signaling 3 (RGS3) is implicated in tumorigenesis, however, its specific role in OC development has not been extensively investigated. Herein, this research elucidated that the overexpression of RGS3 in OC correlates with adverse clinical pathological features and tumor progression. Furthermore, we demonstrated that silencing RGS3 promotes apoptosis, effectively inhibiting tumor growth and metastasis. Additionally, our findings reveal that RGS3 enhances oncogenic activity by activating the Transforming Growth Factor-beta (TGF-β) pathway and corresponding epithelial-mesenchymal transition (EMT). The in-depth mechanism lies in the RGS3 facilitating the phosphorylation of SMAD2/3 by directly interacting with AT-rich interactive domain-containing protein 3B (ARID3B), which ultimately drives OC cell proliferation and metastasis. Therefore, our results position RGS3 as a significant prognostic biomarker and tumor-promoting factor in OC, underscoring the pivotal role of the RGS3/TGF-β/EMT signaling pathway in the pathogenesis of this malignancy. Biological sciences/Cancer Biological sciences/Molecular biology Full Text Additional Declarations There is no duality of interest Supplementary Files originalwesternblots.pdf Original western blots supplementarymaterials.pdf Supplementary material Cite Share Download PDF Status: Published Journal Publication published 02 Jun, 2025 Read the published version in Cell Death Discovery → Version 1 posted 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 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-5307214","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":371684717,"identity":"aad08803-fc28-4853-8e42-7e95af59a940","order_by":0,"name":"Jinhua Zhou","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAt0lEQVRIiWNgGAWjYBACxgaGNCBhw8PP3kCaljQZyZ4DxFvEBtRy2MbghgOR6pn7Dzx7+HPHeR6GGwyMHz7mEOOwGQnpBpJnbvMwzm5glpy5jSgtDGkShm23eZhlDrAx8xKlpf9AmkRi2zkeNokEYrU0JKRJHGw7wMNDvJYZCWmSjW3JPBI8B5uJ84th/5k0yZ9tdvb2x5sPfvhIlJYGngS4G4lQDwTyDOwHiFM5CkbBKBgFIxcAAOVCNjdtPtLlAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-1163-002X","institution":"The First Affiliated Hospital of Soochow University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Jinhua","middleName":"","lastName":"Zhou","suffix":""},{"id":371684718,"identity":"d6ef8133-a06f-47f2-8d0b-34aad68b8afa","order_by":1,"name":"Zizhao Wang","email":"","orcid":"","institution":"The First Affiliated Hospital of Soochow University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zizhao","middleName":"","lastName":"Wang","suffix":""},{"id":371684719,"identity":"dd722aa0-5787-4cc8-8aed-5f25210ecdec","order_by":2,"name":"HuaTing Sun","email":"","orcid":"","institution":"The First Affiliated Hospital of Soochow University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"HuaTing","middleName":"","lastName":"Sun","suffix":""},{"id":371684720,"identity":"4f8512fa-a65d-4e9f-8386-c15f557e081c","order_by":3,"name":"Shunpeng Zhu","email":"","orcid":"","institution":"The First Affiliated Hospital of Soochow University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Shunpeng","middleName":"","lastName":"Zhu","suffix":""},{"id":371684721,"identity":"0644d56a-bb16-476d-9c58-7d2272ef0837","order_by":4,"name":"Fang Wang","email":"","orcid":"","institution":"The First Affiliated Hospital of Soochow University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fang","middleName":"","lastName":"Wang","suffix":""},{"id":371684722,"identity":"b29e2497-aeb1-478d-b081-bdb30d7b69c6","order_by":5,"name":"Quan Li","email":"","orcid":"","institution":"The First Affiliated Hospital of Soochow University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Quan","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2024-10-21 23:20:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5307214/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5307214/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41420-025-02536-3","type":"published","date":"2025-06-02T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":83811476,"identity":"35871420-3af3-46bd-b965-246ba71939ba","added_by":"auto","created_at":"2025-06-03 07:05:45","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2577518,"visible":true,"origin":"","legend":"Article File","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5307214/v1_covered_721cdbd5-8e12-48a1-a585-0f3fd77c2a2e.pdf"},{"id":70519387,"identity":"95139e88-fc6b-4ca2-b9f2-ea42cc9689c2","added_by":"auto","created_at":"2024-12-04 03:13:17","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":630660,"visible":true,"origin":"","legend":"Original western blots","description":"","filename":"originalwesternblots.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5307214/v1/4415914747c639079c1f0750.pdf"},{"id":70519388,"identity":"a0992f9b-c420-4c82-ac01-bc579a2a10c4","added_by":"auto","created_at":"2024-12-04 03:13:17","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":375591,"visible":true,"origin":"","legend":"Supplementary material","description":"","filename":"supplementarymaterials.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5307214/v1/d400346582bd487a64de1cea.pdf"}],"financialInterests":"There is no duality of interest","formattedTitle":"RGS3 functions as a tumor promoter by facilitating the activation of the TGF-β signaling pathway and promoting EMT in ovarian cancer.","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":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"cell-death-discovery","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"cddiscovery","sideBox":"Learn more about [Cell Death Discovery](http://www.nature.com/cddiscovery/)","snPcode":"41420","submissionUrl":"https://mts-cddiscovery.nature.com/","title":"Cell Death Discovery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5307214/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5307214/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Ovarian cancer (OC) is one of the most common and lethal solid malignancies among women, with its incidence steadily rising. Despite substantial advancements in OC research, its pathogenesis remains largely elusive. Recent studies indicate that the regulator of G protein signaling 3 (RGS3) is implicated in tumorigenesis, however, its specific role in OC development has not been extensively investigated. Herein, this research elucidated that the overexpression of RGS3 in OC correlates with adverse clinical pathological features and tumor progression. Furthermore, we demonstrated that silencing RGS3 promotes apoptosis, effectively inhibiting tumor growth and metastasis. Additionally, our findings reveal that RGS3 enhances oncogenic activity by activating the Transforming Growth Factor-beta (TGF-β) pathway and corresponding epithelial-mesenchymal transition (EMT). The in-depth mechanism lies in the RGS3 facilitating the phosphorylation of SMAD2/3 by directly interacting with AT-rich interactive domain-containing protein 3B (ARID3B), which ultimately drives OC cell proliferation and metastasis. Therefore, our results position RGS3 as a significant prognostic biomarker and tumor-promoting factor in OC, underscoring the pivotal role of the RGS3/TGF-β/EMT signaling pathway in the pathogenesis of this malignancy.","manuscriptTitle":"RGS3 functions as a tumor promoter by facilitating the activation of the TGF-β signaling pathway and promoting EMT in ovarian cancer.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-04 03:13:12","doi":"10.21203/rs.3.rs-5307214/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"
[email protected]","identity":"cell-death-discovery","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"cddiscovery","sideBox":"Learn more about [Cell Death Discovery](http://www.nature.com/cddiscovery/)","snPcode":"41420","submissionUrl":"https://mts-cddiscovery.nature.com/","title":"Cell Death Discovery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2973c443-590d-4b9a-a192-b87c80dbe1ad","owner":[],"postedDate":"December 4th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":39554073,"name":"Biological sciences/Cancer"},{"id":39554074,"name":"Biological sciences/Molecular biology"}],"tags":[],"updatedAt":"2025-06-03T07:05:34+00:00","versionOfRecord":{"articleIdentity":"rs-5307214","link":"https://doi.org/10.1038/s41420-025-02536-3","journal":{"identity":"cell-death-discovery","isVorOnly":false,"title":"Cell Death Discovery"},"publishedOn":"2025-06-02 04:00:00","publishedOnDateReadable":"June 2nd, 2025"},"versionCreatedAt":"2024-12-04 03:13:12","video":"","vorDoi":"10.1038/s41420-025-02536-3","vorDoiUrl":"https://doi.org/10.1038/s41420-025-02536-3","workflowStages":[]},"version":"v1","identity":"rs-5307214","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5307214","identity":"rs-5307214","version":["v1"]},"buildId":"zQwnuV7TCBrMSSSToR1PI","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
Text is read by the "Ask this paper" AI Q&A widget below.
Extraction quality varies by source — PMC NXML preserves structure
cleanly, OA-HTML may include some navigation residue, and OA-PDF can
have broken hyphenation. The publisher copy
(via DOI)
is the canonical version.