Mechanism of Colorectal Cancer Development under Exposure to Synthetic Phenolic Antioxidants Based on Network Toxicology and Molecular Docking

Mechanism of Colorectal Cancer Development under Exposure to Synthetic Phenolic Antioxidants Based on Network Toxicology and Molecular Docking | 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 Mechanism of Colorectal Cancer Development under Exposure to Synthetic Phenolic Antioxidants Based on Network Toxicology and Molecular Docking Yifei Shi, Dong Niu, Chunhui Jin This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7207120/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: Synthetic phenolic antioxidants (SPAs) find widespread application in a broad range of industries and everyday consumer products, posing potential health risks. However, the mechanisms linking SPAs to colorectal cancer (CRC) development remain unclear. We explored the underlying mechanisms and key targets of CRC under SPA exposure via network toxicology and molecular docking. Methods: Initially, we screened SPAs with carcinogenic risks, and identified potential targets from Swiss Target Prediction, SEA, Gene Cards, and TTD. Then a total of 222 common targets between SPAs and CRC were identified via Venn diagram analysis. We constructed a protein-protein interaction (PPI) network while hub genes were identified by Cytoscape software. GO and KEGG enrichment analysis were performed. We used RNA-seq data from the TCGA database to assess the expression differences and diagnostic values of hub genes. We finally conducted molecular docking analysis to analyze the interaction between the compounds and proteins. Results: The PPI network pinpointed hub genes such as SRC, MAPK1, HSP90AA1, EGFR, and ESR1. These genes are involved in PI3K-Akt, MAPK, TNF, and VEGF signaling pathways. Differential expression analysis revealed that ESR1, HSP90AA1, and HRAS were significantly overexpressed in CRC tissues with diagnostic potential. There is no doubt that AO245 had the strongest binding energy with AKT1 and SHC1 by molecular docking, suggesting they may be key targets for SPAs-mediated carcinogenesis. Conclusions： SPAs may promote CRC through multiple targets related to cell proliferation, inflammation, and oxidative stress. Hub genes like ESR1 could serve as potential biomarkers, and proteins like AKT1 and SHC1 could be intervention targets. Network toxicology Synthetic phenolic antioxidants Colorectal cancer Molecular docking Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryTable1.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. 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-7207120","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":504412015,"identity":"b7434d69-a60a-4126-b05a-92f64b4d91b6","order_by":0,"name":"Yifei Shi","email":"","orcid":"","institution":"Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yifei","middleName":"","lastName":"Shi","suffix":""},{"id":504412016,"identity":"f2d99327-8a50-43f7-9523-36b2dda800de","order_by":1,"name":"Dong Niu","email":"","orcid":"","institution":"Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Dong","middleName":"","lastName":"Niu","suffix":""},{"id":504412017,"identity":"5a0cf6d0-c099-40c2-8325-b75c6a90f1aa","order_by":2,"name":"Chunhui Jin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5UlEQVRIiWNgGAWjYLCCBIMaOQaGA2A2YwNRWj4UHDMmTQvjjA/MiTCVhLUY3Eh/Js1jwJa+nfGM4acbDDayGw4wP3uAV8uZA2lALTK5OxvOGEvnMKQZbzjAZm6AT4vZ8YZjIFtyNxw4Y8acw3A4ccMBHjYJvFoOM7YBtTCnG0C0/CdCy/FmNskZBswJUC0HCGuxP3OM2eKDwTHDDQeOFUvnGCQbzzzMZoZXi+SM9Ic3Ev7UyBvcOLzxc06FnWzf8eZneLUAAQtEgcQBIAEKKmYC6kFKPoAp/gbCSkfBKBgFo2BkAgD52UxBNkbXBQAAAABJRU5ErkJggg==","orcid":"","institution":"Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine","correspondingAuthor":true,"prefix":"","firstName":"Chunhui","middleName":"","lastName":"Jin","suffix":""}],"badges":[],"createdAt":"2025-07-24 15:38:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7207120/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7207120/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90886980,"identity":"4e2dd6a6-cd60-4b06-b7e8-1368ec835dfe","added_by":"auto","created_at":"2025-09-09 10:17:15","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1169494,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7207120/v1_covered_ef7a3af1-5129-4b0b-a9e5-9e170242b511.pdf"},{"id":89784011,"identity":"c0e0fe0d-5f6d-4ecf-bda0-8fdd6196078f","added_by":"auto","created_at":"2025-08-25 03:24:26","extension":"xlsx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":12361,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7207120/v1/b1d19563d59e778144af2fe7.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Mechanism of Colorectal Cancer Development under Exposure to Synthetic Phenolic Antioxidants Based on Network Toxicology and Molecular Docking","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":"Network toxicology, Synthetic phenolic antioxidants, Colorectal cancer, Molecular docking","lastPublishedDoi":"10.21203/rs.3.rs-7207120/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7207120/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Synthetic phenolic antioxidants (SPAs) find widespread application in a broad range of industries and everyday consumer products, posing potential health risks. However, the mechanisms linking SPAs to colorectal cancer (CRC) development remain unclear. We explored the underlying mechanisms and key targets of CRC under SPA exposure via network toxicology and molecular docking.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eInitially, we screened SPAs with carcinogenic risks, and identified potential targets from Swiss Target Prediction, SEA, Gene Cards, and TTD. Then a total of 222 common targets between SPAs and CRC were identified via Venn diagram analysis. We constructed a protein-protein interaction (PPI) network while hub genes were identified by Cytoscape software. GO and KEGG enrichment analysis were performed. We used RNA-seq data from the TCGA database to assess the expression differences and diagnostic values of hub genes. We finally conducted molecular docking analysis to analyze the interaction between the compounds and proteins.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThe PPI network pinpointed hub genes such as SRC, MAPK1, HSP90AA1, EGFR, and ESR1. These genes are involved in PI3K-Akt, MAPK, TNF, and VEGF signaling pathways. Differential expression analysis revealed that ESR1, HSP90AA1, and HRAS were significantly overexpressed in CRC tissues with diagnostic potential. There is no doubt that AO245 had the strongest binding energy with AKT1 and SHC1 by molecular docking, suggesting they may be key targets for SPAs-mediated carcinogenesis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions：\u003c/strong\u003eSPAs may promote CRC through multiple targets related to cell proliferation, inflammation, and oxidative stress. Hub genes like ESR1 could serve as potential biomarkers, and proteins like AKT1 and SHC1 could be intervention targets.\u003c/p\u003e","manuscriptTitle":"Mechanism of Colorectal Cancer Development under Exposure to Synthetic Phenolic Antioxidants Based on Network Toxicology and Molecular Docking","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-25 03:24:21","doi":"10.21203/rs.3.rs-7207120/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":"becb7f48-c5f1-472d-bb74-20b228f4325f","owner":[],"postedDate":"August 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-09T10:09:04+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-25 03:24:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7207120","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7207120","identity":"rs-7207120","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}