Exosome-Derived LncRNA MIR4435-2HG Suppresses Malignant Phenotypes and Brain Metastasis in Small Cell Lung Cancer

Exosome-Derived LncRNA MIR4435-2HG Suppresses Malignant Phenotypes and Brain Metastasis in Small Cell Lung 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 Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Exosome-Derived LncRNA MIR4435-2HG Suppresses Malignant Phenotypes and Brain Metastasis in Small Cell Lung Cancer Xuanming Mao, Yingze Zhu, Ye Jin, Weinan Yao, Jun qing Gan, Yan na Bi, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8510151/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 14 You are reading this latest preprint version Abstract Background:Brain metastasis in small cell lung cancer(SCLC) is a significant factor leading to poor prognosis in patients.To investigate the role of exosomal lncRNA MIR4435-2HG in the development and progression of brain metastasis in small cell lung cancer , and its effects on malignant phenotypes including proliferation, migration, and invasion in Small Cell Lung Cancer . Methods:Transcriptome sequencing and bioinformatics analysis were utilized to identify key candidate lncRNAs in Small Cell Lung Cancer, followed by Gene ontology analysis and Pathway analysis. The expression of exosomal lncRNA MIR4435-2HG was measured using quantitative real-time polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization assay, and its clinicopathological characteristics were analyzed. Following the assessment of cellular exosome uptake via confocal fluorescence microscopy, the effects of exosomal lncRNA MIR4435-2HG overexpression on proliferation, invasion, and migration in small cell lung cancer cells were evaluated using Cell Counting Kit-8 (CCK-8), colony formation assay, Transwell migration and invasion assays, and scratch assay. Results:Transcriptome sequencing combined with database analysis revealed differential expression of exosomal lncRNA MIR4435-2HG in Small Cell Lung Cancer patients and small cell lung cancer patients with brain metastasis. Gene ontology analysis predicted its enrichment in focal adhesion and cell-matrix adhesion processes, while subsequent kyoto encyclopedia of genes and genomes pathway analysis demonstrated its close association with cancer-related proteoglycan signaling pathways. RT-qPCR and tissue fluorescence in situ hybridization assays confirmed that exosomal lncRNA MIR4435-2HG exhibits low expression in plasma exosomes, extracellular vesicles, and tissues of patients with small cell lung cancer and small cell lung cancer brain metastasis; this low expression correlates with the clinical stage of small cell lung cancer and brain metastasis. Furthermore, overexpression of exosome-derived lncRNA MIR4435-2HG suppressed the proliferation, migration, and invasion of small cell lung cancer cells. Conclusion:Exosomal lncRNA MIR4435-2HG inhibits malignant phenotypes in small cell lung cancer and suppresses brain metastasis. Small cell lung cancer Brain metastasis Exosomes lncRNA MIR4435-2HG Proliferation Migration Invasion Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 10 Feb, 2026 Reviews received at journal 09 Feb, 2026 Reviews received at journal 09 Feb, 2026 Reviews received at journal 08 Feb, 2026 Reviewers agreed at journal 08 Feb, 2026 Reviewers agreed at journal 07 Feb, 2026 Reviewers agreed at journal 05 Feb, 2026 Reviewers agreed at journal 16 Jan, 2026 Reviewers agreed at journal 14 Jan, 2026 Reviewers invited by journal 13 Jan, 2026 Editor invited by journal 13 Jan, 2026 Editor assigned by journal 09 Jan, 2026 Submission checks completed at journal 08 Jan, 2026 First submitted to journal 08 Jan, 2026 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. 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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-8510151","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":575617325,"identity":"91e37a69-0222-4860-90e8-bf7b84bd76f6","order_by":0,"name":"Xuanming Mao","email":"","orcid":"","institution":"North China University of Science and Technology Affiliated Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xuanming","middleName":"","lastName":"Mao","suffix":""},{"id":575617338,"identity":"d1b49356-db50-4abf-a58d-5b809ef4f229","order_by":1,"name":"Yingze Zhu","email":"","orcid":"","institution":"North China University of 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Cancer","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Small cell lung cancer, Brain metastasis, Exosomes, lncRNA MIR4435-2HG, Proliferation, Migration, Invasion","lastPublishedDoi":"10.21203/rs.3.rs-8510151/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8510151/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Background:Brain metastasis in small cell lung cancer(SCLC) is a significant factor leading to poor prognosis in patients.To investigate the role of exosomal lncRNA MIR4435-2HG in the development and progression of brain metastasis in small cell lung cancer , and its effects on malignant phenotypes including proliferation, migration, and invasion in Small Cell Lung Cancer . Methods:Transcriptome sequencing and bioinformatics analysis were utilized to identify key candidate lncRNAs in Small Cell Lung Cancer, followed by Gene ontology analysis and Pathway analysis. The expression of exosomal lncRNA MIR4435-2HG was measured using quantitative real-time polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization assay, and its clinicopathological characteristics were analyzed. Following the assessment of cellular exosome uptake via confocal fluorescence microscopy, the effects of exosomal lncRNA MIR4435-2HG overexpression on proliferation, invasion, and migration in small cell lung cancer cells were evaluated using Cell Counting Kit-8 (CCK-8), colony formation assay, Transwell migration and invasion assays, and scratch assay. Results:Transcriptome sequencing combined with database analysis revealed differential expression of exosomal lncRNA MIR4435-2HG in Small Cell Lung Cancer patients and small cell lung cancer patients with brain metastasis. Gene ontology analysis predicted its enrichment in focal adhesion and cell-matrix adhesion processes, while subsequent kyoto encyclopedia of genes and genomes pathway analysis demonstrated its close association with cancer-related proteoglycan signaling pathways. RT-qPCR and tissue fluorescence in situ hybridization assays confirmed that exosomal lncRNA MIR4435-2HG exhibits low expression in plasma exosomes, extracellular vesicles, and tissues of patients with small cell lung cancer and small cell lung cancer brain metastasis; this low expression correlates with the clinical stage of small cell lung cancer and brain metastasis. Furthermore, overexpression of exosome-derived lncRNA MIR4435-2HG suppressed the proliferation, migration, and invasion of small cell lung cancer cells. Conclusion:Exosomal lncRNA MIR4435-2HG inhibits malignant phenotypes in small cell lung cancer and suppresses brain metastasis.","manuscriptTitle":"Exosome-Derived LncRNA MIR4435-2HG Suppresses Malignant Phenotypes and Brain Metastasis in Small Cell Lung Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-19 19:05:14","doi":"10.21203/rs.3.rs-8510151/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-10T05:17:25+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-09T09:42:31+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-09T05:48:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-08T11:25:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"51677737468666268660590648441379290457","date":"2026-02-08T11:13:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"306115761889138973308834324604187103965","date":"2026-02-07T10:07:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"174296287359859885887581298966468030928","date":"2026-02-05T08:15:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"88367060472231226027533675487280493652","date":"2026-01-16T12:47:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"220282313296600000700704140122365593878","date":"2026-01-14T17:16:12+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-14T04:30:36+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-13T14:40:50+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-09T10:43:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-09T04:51:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Oncology","date":"2026-01-09T04:45:59+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a2e1c217-a32f-4dc6-ad4d-fc0a71a7859e","owner":[],"postedDate":"January 19th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-01T06:38:46+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-19 19:05:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8510151","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8510151","identity":"rs-8510151","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}