An Integrated Analysis of RNA Sequencing and Molecular Docking Reveal EIF2AK2, IFIT1, and STAT1 as Key Targets of EGCG in Nasopharyngeal Carcinoma

An Integrated Analysis of RNA Sequencing and Molecular Docking Reveal EIF2AK2, IFIT1, and STAT1 as Key Targets of EGCG in Nasopharyngeal Carcinoma | 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 An Integrated Analysis of RNA Sequencing and Molecular Docking Reveal EIF2AK2, IFIT1, and STAT1 as Key Targets of EGCG in Nasopharyngeal Carcinoma Yuhang Yang, Guangxu Xuan, Zhang Feng, Ming Deng, Fangxian Liu, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6726357/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background:Epigallocatechin gallate (EGCG), a frequently studied catechin in green tea, has been shown to be involved in the antiproliferation and apoptosis of human Nasopharyngeal carcinoma (NPC) cells. However, the pharmacological targets and mechanism by which EGCG can combat NPC patients remain to be studied in detail. Methods:Experiments with cell lines and subsequent RNA sequencing, network pharmacology, molecular docking and molecular dynamics simulations were employed to elucidate the molecular mechanisms underlying the therapeutic effects of EGCG on NPC, with a focus on identifying potential therapeutic targets. Additionally, our assessment of the relationships between key target genes and NPC encompassed single-cell RNA sequencing (scRNA-seq) analysis as well as Mendelian Randomization (MR) analyses. Results:Analysis of the Gene Expression Omnibus (GEO) database and RNA sequencing of EGCG-treated NPC (HK-1) cells identified 165 potential targets associated with both EGCG and NPC. Network analysis using the STRING database and Cytoscape software revealed ten core targets, including EIF2AK2, IFIT1 and STAT1. KEGG pathway and Gene Ontology (GO) enrichment analyses highlighted key biological processes and signalling pathways involved in EGCG-mediated NPC treatment. Molecular docking simulations using AutoDock software confirmed strong binding interactions between EGCG and these core targets. Additionally, molecular dynamics simulations refined and validated the binding modes, providing a detailed molecular-level understanding. Finally, differential expression profiling of key target genes at the single-cell level demonstrated a concordance with transcriptomic data, while MR analyses validated the causal relationships between these target genes and the risk of NPC. Conclusion:These findings offer a theoretical basis for the molecular mechanisms underlying EGCG’s therapeutic effects on NPC. The identified core targets may serve as valuable references for drug development and functional additive research related to EGCG. Epigallocatechin-3-gallate Nasopharyngeal carcinoma RNA sequence molecular docking Mendelian Randomization Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryTableS1.xlsx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 30 Jul, 2025 Reviews received at journal 29 Jul, 2025 Reviewers agreed at journal 11 Jul, 2025 Reviews received at journal 10 Jul, 2025 Reviewers agreed at journal 18 Jun, 2025 Reviewers agreed at journal 16 Jun, 2025 Reviewers invited by journal 10 Jun, 2025 Editor assigned by journal 23 May, 2025 Submission checks completed at journal 23 May, 2025 First submitted to journal 22 May, 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. 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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-6726357","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":469237587,"identity":"b767626d-d08d-4760-b3b0-0848d676e494","order_by":0,"name":"Yuhang Yang","email":"","orcid":"","institution":"Affiliated Hospital of Guilin Medical College","correspondingAuthor":false,"prefix":"","firstName":"Yuhang","middleName":"","lastName":"Yang","suffix":""},{"id":469237588,"identity":"495a45d7-abd5-4ac7-9019-d042c088bb16","order_by":1,"name":"Guangxu Xuan","email":"","orcid":"","institution":"Affiliated Hospital of Guilin Medical 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Carcinoma","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":"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":"Epigallocatechin-3-gallate, Nasopharyngeal carcinoma, RNA sequence, molecular docking, Mendelian Randomization","lastPublishedDoi":"10.21203/rs.3.rs-6726357/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6726357/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Background:Epigallocatechin gallate (EGCG), a frequently studied catechin in green tea, has been shown to be involved in the antiproliferation and apoptosis of human Nasopharyngeal carcinoma (NPC) cells. However, the pharmacological targets and mechanism by which EGCG can combat NPC patients remain to be studied in detail.\n \nMethods:Experiments with cell lines and subsequent RNA sequencing, network pharmacology, molecular docking and molecular dynamics simulations were employed to elucidate the molecular mechanisms underlying the therapeutic effects of EGCG on NPC, with a focus on identifying potential therapeutic targets. Additionally, our assessment of the relationships between key target genes and NPC encompassed single-cell RNA sequencing (scRNA-seq) analysis as well as Mendelian Randomization (MR) analyses. \n \nResults:Analysis of the Gene Expression Omnibus (GEO) database and RNA sequencing of EGCG-treated NPC (HK-1) cells identified 165 potential targets associated with both EGCG and NPC. Network analysis using the STRING database and Cytoscape software revealed ten core targets, including EIF2AK2, IFIT1 and STAT1. KEGG pathway and Gene Ontology (GO) enrichment analyses highlighted key biological processes and signalling pathways involved in EGCG-mediated NPC treatment. Molecular docking simulations using AutoDock software confirmed strong binding interactions between EGCG and these core targets. Additionally, molecular dynamics simulations refined and validated the binding modes, providing a detailed molecular-level understanding. Finally, differential expression profiling of key target genes at the single-cell level demonstrated a concordance with transcriptomic data, while MR analyses validated the causal relationships between these target genes and the risk of NPC.\n \nConclusion:These findings offer a theoretical basis for the molecular mechanisms underlying EGCG’s therapeutic effects on NPC. The identified core targets may serve as valuable references for drug development and functional additive research related to EGCG.\n ","manuscriptTitle":"An Integrated Analysis of RNA Sequencing and Molecular Docking Reveal EIF2AK2, IFIT1, and STAT1 as Key Targets of EGCG in Nasopharyngeal Carcinoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-13 16:58:58","doi":"10.21203/rs.3.rs-6726357/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-30T06:06:38+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-30T03:24:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"235697608705994282080924508972742774065","date":"2025-07-11T07:32:36+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-10T13:03:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"338913467948204904202967124105876506807","date":"2025-06-18T06:41:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"338113123829316491783005000896222450240","date":"2025-06-16T09:41:54+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-10T12:49:52+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-23T11:16:40+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-23T11:15:57+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Oncology","date":"2025-05-22T15:16:09+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":"ae5b8786-09ca-4a2f-ab4f-765ed6a5b975","owner":[],"postedDate":"June 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-10T09:41:59+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-13 16:58:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6726357","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6726357","identity":"rs-6726357","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}