RNA Binding Motif Protein RBM41 Promotes Colorectal Tumorigenesis by Impeding the Maturation of NDRG1 Pre-mRNA

RNA Binding Motif Protein RBM41 Promotes Colorectal Tumorigenesis by Impeding the Maturation of NDRG1 Pre-mRNA | 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 RNA Binding Motif Protein RBM41 Promotes Colorectal Tumorigenesis by Impeding the Maturation of NDRG1 Pre-mRNA Yanxin Liu, Jianfeng Mu, Jiming Yu, Qirong Li, Tiantian Li, Qiang Feng, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8521664/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 Background Colorectal cancer (CRC) is a prevalent and highly lethal malignancy whose progression and therapeutic resistance are driven by complex post-transcriptional regulatory mechanisms. RNA-binding motif (RBM) proteins have been demonstrated to play a role in CRC pathogenesis. Methods The functional role of RBM41 was investigated using CRC cell lines, patient-derived organoid (PDO) models, and xenograft tumor experiments in vivo. Molecular mechanisms were explored by examining the interaction between RBM41 and its target mRNA. Results Elevated RBM41 expression in CRC tissues was associated with poor prognosis. Inhibition of RBM41 significantly decreased CRC cell proliferation and induced autophagic cell death and apoptosis. Mechanistically, RBM41 directly binds the 3' untranslated region (3' UTR) of NDRG1 pre-mRNA, inhibiting its processing and reducing mature NDRG1 transcript and protein levels. NDRG1 was found to counteract the oncogenic functions of RBM41, and concurrent knockdown of NDRG1 reversed these effects both in vitro and in vivo. Furthermore, PDO models with high RBM41 expression exhibited increased resistance to 5-fluorouracil, oxaliplatin, and irinotecan. Conclusions RBM41 acts as a key post-transcriptional regulator of CRC progression by repressing NDRG1, highlighting its potential as a therapeutic target in colorectal cancer. RBM41 Colorectal cancer Post-transcriptional regulation NDRG1 Pre-mRNA maturation Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryTables.xlsx 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. 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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-8521664","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":571643072,"identity":"28043718-94ba-480c-b330-43dee941d0d3","order_by":0,"name":"Yanxin Liu","email":"","orcid":"","institution":"First Hospital of Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Yanxin","middleName":"","lastName":"Liu","suffix":""},{"id":571643074,"identity":"7ec012f4-9642-4729-9b17-dbc44eff5f36","order_by":1,"name":"Jianfeng Mu","email":"","orcid":"","institution":"First Hospital of Jilin 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Pre-mRNA","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":"RBM41, Colorectal cancer, Post-transcriptional regulation, NDRG1, Pre-mRNA maturation","lastPublishedDoi":"10.21203/rs.3.rs-8521664/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8521664/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eColorectal cancer (CRC) is a prevalent and highly lethal malignancy whose progression and therapeutic resistance are driven by complex post-transcriptional regulatory mechanisms. RNA-binding motif (RBM) proteins have been demonstrated to play a role in CRC pathogenesis.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe functional role of RBM41 was investigated using CRC cell lines, patient-derived organoid (PDO) models, and xenograft tumor experiments in vivo. Molecular mechanisms were explored by examining the interaction between RBM41 and its target mRNA.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eElevated RBM41 expression in CRC tissues was associated with poor prognosis. Inhibition of RBM41 significantly decreased CRC cell proliferation and induced autophagic cell death and apoptosis. Mechanistically, RBM41 directly binds the 3' untranslated region (3' UTR) of NDRG1 pre-mRNA, inhibiting its processing and reducing mature NDRG1 transcript and protein levels. NDRG1 was found to counteract the oncogenic functions of RBM41, and concurrent knockdown of NDRG1 reversed these effects both in vitro and in vivo. Furthermore, PDO models with high RBM41 expression exhibited increased resistance to 5-fluorouracil, oxaliplatin, and irinotecan.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eRBM41 acts as a key post-transcriptional regulator of CRC progression by repressing NDRG1, highlighting its potential as a therapeutic target in colorectal cancer.\u003c/p\u003e","manuscriptTitle":"RNA Binding Motif Protein RBM41 Promotes Colorectal Tumorigenesis by Impeding the Maturation of NDRG1 Pre-mRNA","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-12 20:49:14","doi":"10.21203/rs.3.rs-8521664/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","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}}],"origin":"","ownerIdentity":"d243d4f3-598b-43ab-921a-617b691b54bf","owner":[],"postedDate":"January 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-29T15:38:44+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-12 20:49:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8521664","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8521664","identity":"rs-8521664","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}