Identification and exploration of potential N6-methylation related mRNAs in endometriosis

In: Research Square · 2024 · vol. 17 · doi:10.21203/rs.3.rs-4509482/v1 · W4399942672
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This study identified six potential m6A-related mRNAs, including VCAM1 and RAP1A, as novel targets for endometriosis treatment and prevention.

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This preprint investigated m6A (N6-methyladenosine) epitranscriptomic dysregulation in endometriosis by using an arraystar m6A-mRNA microarray, followed by biological information analyses and validation using other databases to identify aberrant m6A-related mRNAs and potential therapeutic small molecules. The authors reported 8333 m6A-methylated mRNAs in endometriosis and highlighted several candidate hub m6A-related mRNAs (FN1, VCAM1, RAP1A, BRCA1, CCNA2, and CDK1), noting VCAM1 and RAP1A as the two most important, with pathway enrichment and protein-protein interaction analyses supporting their role. They further used database and computational approaches (including docking) to propose small-molecule agents targeting VCAM1 and RAP1A, and validated candidate mRNA expression in publicly accessible datasets. A key caveat is that the work is a preprint and not peer reviewed, and the abstract does not describe experimental in vivo/in vitro confirmation of drug effects. This paper is centrally about endometriosis — it specifically identifies and prioritizes potential m6A-related mRNAs (including VCAM1 and RAP1A) and candidate therapeutic targets in endometriosis.

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Abstract

Abstract Background: N6-methyladenosine(m6A) modification regulates the processes of RNA splicing, subcellular localization, translation and stability by changing the RNA structure and the interaction between RNA and RNA-binding proteins to ensure the timely and accurate expression of genes. In this study, we investigated m6A-related mRNAs and for the first time explored effective prevention and treatment targets in endometriosis (EM). Methods: By arraystar m6A-mRNA epitranscriptomic microarray, biological information analysis technologies, and validation of other databases, aberrant m6A- related mRNAs were uncovered, as well as efficient therapeutic drugs. Results: FN1, VCAM1, RAP1A, BRCA1, CCNA2 and CDK1 might be vital m6A-related mRNAs, and VCAM1 and RAP1A may be the most important two. A few crucial small-molecule agents supply new views for the treatment of EM. Conclusion: These results demonstrated novel insights into m6A modification of EM and revealed potential biomarkers and precision medicine strategies for EM.
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Identification and exploration of potential N6-methylation related mRNAs in endometriosis | 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 Identification and exploration of potential N6-methylation related mRNAs in endometriosis Yanan He, Chengcheng Ren, Liang Lei, Zihan Hu, Jixin Li, Yan Cheng, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4509482/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 3 You are reading this latest preprint version Abstract Background: N6-methyladenosine(m6A) modification regulates the processes of RNA splicing, subcellular localization, translation and stability by changing the RNA structure and the interaction between RNA and RNA-binding proteins to ensure the timely and accurate expression of genes. In this study, we investigated m6A-related mRNAs and for the first time explored effective prevention and treatment targets in endometriosis (EM). Methods: By arraystar m6A-mRNA epitranscriptomic microarray, biological information analysis technologies, and validation of other databases, aberrant m6A- related mRNAs were uncovered, as well as efficient therapeutic drugs. Results: FN1, VCAM1, RAP1A, BRCA1, CCNA2 and CDK1 might be vital m6A-related mRNAs, and VCAM1 and RAP1A may be the most important two. A few crucial small-molecule agents supply new views for the treatment of EM. Conclusion: These results demonstrated novel insights into m6A modification of EM and revealed potential biomarkers and precision medicine strategies for EM. endometriosis m6A-related mRNAs VCAM1 RAP1A therapeuticdrugs Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Full Text Additional Declarations No competing interests reported. Table 1 is available in the Supplementary Files section. Supplementary Files Table1.docx Cite Share Download PDF Status: Under Review Version 1 posted Editor assigned by journal 10 Jun, 2024 Submission checks completed at journal 10 Jun, 2024 First submitted to journal 31 May, 2024 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-4509482","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":312505993,"identity":"555ee89b-87df-41ae-a8b3-5dd9de0aafa5","order_by":0,"name":"Yanan He","email":"","orcid":"","institution":"the First Affiliated Hospital of Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yanan","middleName":"","lastName":"He","suffix":""},{"id":312505995,"identity":"c5d87271-ca3d-4097-9ad6-75f29dfd9c09","order_by":1,"name":"Chengcheng Ren","email":"","orcid":"","institution":"the First Affiliated Hospital of Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chengcheng","middleName":"","lastName":"Ren","suffix":""},{"id":312505998,"identity":"671454bc-22b2-4a5e-8153-c0e4efe1239e","order_by":2,"name":"Liang Lei","email":"","orcid":"","institution":"Heilongjiang Provincial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Liang","middleName":"","lastName":"Lei","suffix":""},{"id":312506001,"identity":"5c80f2b3-a121-42cc-8ca7-71882e7e8d3a","order_by":3,"name":"Zihan Hu","email":"","orcid":"","institution":"the First Affiliated Hospital of Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zihan","middleName":"","lastName":"Hu","suffix":""},{"id":312506005,"identity":"078f9f79-fd69-4a69-97f4-e71efd36afbb","order_by":4,"name":"Jixin Li","email":"","orcid":"","institution":"Shengjing Hospital of China Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jixin","middleName":"","lastName":"Li","suffix":""},{"id":312506007,"identity":"9391c4b7-3009-4a13-8baa-70aebf2433ee","order_by":5,"name":"Yan Cheng","email":"","orcid":"","institution":"the First Affiliated Hospital of Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yan","middleName":"","lastName":"Cheng","suffix":""},{"id":312506009,"identity":"aedadafc-b999-4a88-ac5c-c3c3e17c3e8e","order_by":6,"name":"Liyuan Sun","email":"","orcid":"","institution":"the First Affiliated Hospital of Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Liyuan","middleName":"","lastName":"Sun","suffix":""},{"id":312506010,"identity":"835e6447-f42b-4c42-ae50-ac2126a295ae","order_by":7,"name":"Guangmei Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIiWNgGAWjYBADHgYJEFUhIcdPopYzFsaSDUTbA9LC2FaRuIGQFvmI5GcPv+bYyMjPbgYy5kkwbmBgfvjoBh4thjfSzI1lt6XxMM45BmJIMJszsBkb5+DTMiPBTFpy22EeZgkwQ4LNsoGHTRq/lvRvQJX/edgkQIw5EjwGBwhokZfIMZP8uO0ADw+Y0SAhQVCLAc+bMmnGbck8EhI5ZdIMxyQMJJsJ+EW+PX2b5M9tdvbyM4CMHzV19f3szQ8f47XlAAMDMw+UA2Ew41EOtqUBGIE/oBw4YxSMglEwCkYBMgAAG9VEQYUcLKwAAAAASUVORK5CYII=","orcid":"","institution":"the First Affiliated Hospital of Harbin Medical University","correspondingAuthor":true,"prefix":"","firstName":"Guangmei","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2024-05-31 14:02:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4509482/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4509482/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":58966578,"identity":"7ec5a309-d763-4b91-8b60-26ec09ddd983","added_by":"auto","created_at":"2024-06-24 18:36:20","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2237743,"visible":true,"origin":"","legend":"\u003cp\u003eIdentification of 8333 m6A-methylated mRNAs in endometriosis. (A) Volcano plot of 8333 m6A-methylated mRNAs. Red, purple and blue data points represent hypermethylated upregulation, hypomethylated upregulation andhypomethylated downregulation, respectively. (B) Identification of 1631hypermethylated-upregulated expressed mRNAs, 219 hypomethylated-upregulatedexpressed mRNAs and 6483 hypomethylated-downregulated expressed mRNAs inendometriosis. (C) The heatmap of differential m6A methylation levels in the ectopicand normal endometrium. Each row represents a m6A-methylated mRNAs and eachcolumn represents a sample. NE: normal endometrium; EI: Ectopic endometrium.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4509482/v1/ebbbbaeb94d229f65baae429.png"},{"id":58966333,"identity":"7645efb6-1c1f-4ecf-b5fa-d9b734c0f521","added_by":"auto","created_at":"2024-06-24 18:28:20","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":11661308,"visible":true,"origin":"","legend":"\u003cp\u003eGene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analyses (KEGG). (A-B) GO analysis of the top 10 hypermethylated m6AmRNAs (A) and hypomethylated m6A mRNAs (B) in endometriosis. biological processes (BP), cellular components (CC) and molecular function (MF)(p \u0026lt;0.05). (C-D) Kyoto Encyclopedia of Genes and Genomes pathways analysis of 1631hypermethylated m6A mRNAs (C) and 6702 hypomethylated m6A mRNAs (D) inendometriosis (p \u0026lt; 0.05).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4509482/v1/7c7a65f8b228f4c2d9808d18.png"},{"id":58967110,"identity":"f00f4c67-2d38-43aa-9766-f82056706d0c","added_by":"auto","created_at":"2024-06-24 18:52:20","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1067245,"visible":true,"origin":"","legend":"\u003cp\u003eThe protein-protein interactionnetwork(PPI), module and identificationof hub m6A mRNAs. (A) The PPI network of hypermethylated-upregulated m6AmRNAs. (B) The Venn picture of the top ten hypermethylated-upregulated m6AmRNAs. (C) The PPI network of hypomethylated-upregulated m6A mRNAs. (D) ThePPI network of hypomethylated-downregulated m6A mRNAs. (E) The Venn picture of the top ten hypomethylated-downregulated m6A mRNAs. (F) The expression of hub genes in NE and EI tissues(3V3)\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4509482/v1/1db7ee3f0b18cba8081251d0.png"},{"id":58966332,"identity":"22bf6eac-7f60-435c-85e9-c0eb7f7433da","added_by":"auto","created_at":"2024-06-24 18:28:20","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":883675,"visible":true,"origin":"","legend":"\u003cp\u003eAnalysis and validation of the hub m6A mRNAs in two databases. (A) Validation the hub m6A mRNAs in the publicly accessible ENDOMETTurkuEndometriosis Database. (B) Validation in the GSE5108 dataset. (C) The ROCanalysis of the 8 candidate m6A mRNAs.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-4509482/v1/ced71a71bb6f8e3a18b641ba.png"},{"id":58966327,"identity":"6745c258-c10f-4f9f-a579-a00e844e3c45","added_by":"auto","created_at":"2024-06-24 18:28:20","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":131156,"visible":true,"origin":"","legend":"\u003cp\u003e3D conformers of the candidate therapeutic agents. (A) The 3Dstructures of the five chemicals. (B) Chemical compounds acting on VCAM1andRAP1A in the STITCH database. (C-D) Docking of VCAM1 and therapeutic. (E) Docking of RAP1A and therapeutic.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-4509482/v1/3810c5da71756c139e6650a5.png"},{"id":58966888,"identity":"2e28f71e-c1c2-443b-a27e-b9fd54f83a50","added_by":"auto","created_at":"2024-06-24 18:44:20","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":223059,"visible":true,"origin":"","legend":"\u003cp\u003eExpression of VCAM1 and RAP1A in clinical tissues (12v12). (A) VCAM1. 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