N 6 -methyladenosine modified GNAI2 accelerates the tumorigenesis of gastric cancer by inhibiting ferroptosis

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N 6 -methyladenosine modified GNAI2 accelerates the tumorigenesis of gastric cancer by inhibiting ferroptosis | 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 N 6 -methyladenosine modified GNAI2 accelerates the tumorigenesis of gastric cancer by inhibiting ferroptosis Yu Han, Sha Liu, Zhao Kun, Huang yubin This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8818761/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Emerging evidence had indicated that ferroptosis and m 6 A modification play important roles in mRNA transcription. However, the role of m 6 A modified GNAI2 on the gastric cancer (GC) ferroptosis and tumorigenesis is still unclear. In this study, the elevated GNAI2 expression indicated a poor prognosis of GC specimens and GNAI2 accelerated the GC tumorigenesis in vitro . Functionally, transmission electron microscopy, iron ion (Fe 2+ ) concentration, fluorescent probe FerroOrange and lipid peroxidation analysis revealed that GNAI2 could repress the ferroptosis of GC. Mechanistically, GNAI2 was modified by m 6 A reader hnRNPA2B1, and hnRNPA2B1 enhanced the stability of GNAI2 mRNA by m 6 A manner. In vivo , GNAI2 silencing repressed the GC tumor growth and accelerated the Fe 2+ concentration in tumor tissue. Overall, these data concluded that m 6 A modified GNAI2 accelerated the tumorigenesis of gastric cancer by inhibiting ferroptosis, which provides a novel insight for GC treatment. gastric cancer GNAI2 N6-methyladenosine hnRNPA2B1 ferroptosis Full Text Additional Declarations No competing interests reported. Supplementary Files Figure5GBoriginalimages.pptx Cite Share Download PDF Status: Posted 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 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-8818761","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":606488489,"identity":"fce941b8-55bb-4a21-b710-8922ed3d8cfd","order_by":0,"name":"Yu Han","email":"","orcid":"","institution":"Meizhou People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Han","suffix":""},{"id":606488490,"identity":"a05e5ff8-0cb5-44a7-ae51-4c95ba668d39","order_by":1,"name":"Sha Liu","email":"","orcid":"","institution":"Meizhou People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Sha","middleName":"","lastName":"Liu","suffix":""},{"id":606488499,"identity":"1a0cdadf-8739-4f1e-8967-70e911b4a0ab","order_by":2,"name":"Zhao Kun","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhao","middleName":"","lastName":"Kun","suffix":""},{"id":606488507,"identity":"5d85e903-3bd9-4792-98ea-c55c5f1e6508","order_by":3,"name":"Huang yubin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzElEQVRIiWNgGAWjYDAC5gOMDz4Y2MixsTcfIFILWwKz4YyCNGM+nmMJRGthk+b5cChxnkSOAnE6+Nl4zKR5DA6ktzHkMDD8qNhGWItkG4+x5RyDO7ltDGcPMPacuU1Yi8H9HsMbbwye5bYx9iUwM7YRocX+GI+BBI/B4XQ2Zh4D4rQYsPEYSQK1JLCxEatF4hhbseEMgzTDNh62hINE+YW/jXnjgw9/bOTl5z8++OBHBRFaGBg4DODMA8SoBwL2B0QqHAWjYBSMghELACslOtALpEwlAAAAAElFTkSuQmCC","orcid":"","institution":"The Second Affiliated Hospital of Guangxi Medical University","correspondingAuthor":true,"prefix":"","firstName":"Huang","middleName":"","lastName":"yubin","suffix":""}],"badges":[],"createdAt":"2026-02-08 02:53:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8818761/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8818761/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108182664,"identity":"61ea53bc-dfef-4a36-9ae6-be123aa929ae","added_by":"auto","created_at":"2026-04-30 08:59:29","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1162294,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8818761/v1_covered_65b3e0c7-5bca-4187-928c-1a474fff7d10.pdf"},{"id":104735305,"identity":"29c16bae-7bdc-4c5b-be8d-556e62cbdc98","added_by":"auto","created_at":"2026-03-16 15:13:30","extension":"pptx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":402413,"visible":true,"origin":"","legend":"","description":"","filename":"Figure5GBoriginalimages.pptx","url":"https://assets-eu.researchsquare.com/files/rs-8818761/v1/e82bd4dabbef9e96b0913840.pptx"}],"financialInterests":"No competing interests reported.","formattedTitle":"N 6 -methyladenosine modified GNAI2 accelerates the tumorigenesis of gastric cancer by inhibiting ferroptosis","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"gastric cancer, GNAI2, N6-methyladenosine, hnRNPA2B1, ferroptosis","lastPublishedDoi":"10.21203/rs.3.rs-8818761/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8818761/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eEmerging evidence had indicated that ferroptosis and m\u003csup\u003e6\u003c/sup\u003eA modification play important roles in mRNA transcription. However, the role of m\u003csup\u003e6\u003c/sup\u003eA modified GNAI2 on the gastric cancer (GC) ferroptosis and tumorigenesis is still unclear. In this study, the elevated GNAI2 expression indicated a poor prognosis of GC specimens and GNAI2 accelerated the GC tumorigenesis in \u003cem\u003evitro\u003c/em\u003e. Functionally, transmission electron microscopy, iron ion (Fe\u003csup\u003e2+\u003c/sup\u003e) concentration, fluorescent probe FerroOrange and lipid peroxidation analysis revealed that GNAI2 could repress the ferroptosis of GC. Mechanistically, GNAI2 was modified by m\u003csup\u003e6\u003c/sup\u003eA reader hnRNPA2B1, and hnRNPA2B1 enhanced the stability of GNAI2 mRNA by m\u003csup\u003e6\u003c/sup\u003eA manner. In \u003cem\u003evivo\u003c/em\u003e, GNAI2 silencing repressed the GC tumor growth and accelerated the Fe\u003csup\u003e2+\u003c/sup\u003e concentration in tumor tissue. 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