Exploring the mechanism of action of PPCPs on thyroid cancer based on network toxicology, Mendelian analysis and molecular docking

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Abstract

Abstract Pharmaceuticals and personal care products (PPCPs) are ubiquitous environmental contaminants linked to various adverse health outcomes, and thyroid cancer (THCA), the most common endocrine malignancy, has a globally increasing incidence. This study aimed to systematically elucidate the molecular mechanisms underlying the effects of 11 prevalent PPCPs on THCA via an integrated bioinformatics approach. Candidate target genes of the 11 PPCPs were retrieved and predicted using authoritative public databases. These genes were subsequently subjected to Mendelian randomization (MR) analysis to identify those with causal links to THCA. By integrating transcriptome data mining and differential expression analysis, key genes with consistent causal relationships and expression patterns were screened. Core targets were prioritized through complementary machine learning approaches and validated using independent external datasets. Functional enrichment analyses, immune infiltration assessment, single-cell RNA sequencing, and molecular docking were further performed to decipher potential regulatory mechanisms. This study delineates the core targets and pivotal molecular pathways underlying PPCP-mediated regulation of THCA progression, providing novel insights into the environmental etiology of THCA. The findings underscore the necessity of enhancing monitoring of PPCP pollution and offer valuable implications for THCA prevention and therapeutic strategy development.
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Exploring the mechanism of action of PPCPs on thyroid cancer based on network toxicology, Mendelian analysis 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 Exploring the mechanism of action of PPCPs on thyroid cancer based on network toxicology, Mendelian analysis and molecular docking Jieming Yang, Baoshan Tang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8750403/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Pharmaceuticals and personal care products (PPCPs) are ubiquitous environmental contaminants linked to various adverse health outcomes, and thyroid cancer (THCA), the most common endocrine malignancy, has a globally increasing incidence. This study aimed to systematically elucidate the molecular mechanisms underlying the effects of 11 prevalent PPCPs on THCA via an integrated bioinformatics approach. Candidate target genes of the 11 PPCPs were retrieved and predicted using authoritative public databases. These genes were subsequently subjected to Mendelian randomization (MR) analysis to identify those with causal links to THCA. By integrating transcriptome data mining and differential expression analysis, key genes with consistent causal relationships and expression patterns were screened. Core targets were prioritized through complementary machine learning approaches and validated using independent external datasets. Functional enrichment analyses, immune infiltration assessment, single-cell RNA sequencing, and molecular docking were further performed to decipher potential regulatory mechanisms. This study delineates the core targets and pivotal molecular pathways underlying PPCP-mediated regulation of THCA progression, providing novel insights into the environmental etiology of THCA. The findings underscore the necessity of enhancing monitoring of PPCP pollution and offer valuable implications for THCA prevention and therapeutic strategy development. PPCPs Thyroid cancer Mendelian randomization Network Toxicology Molecular Docking Full Text Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions 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. 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