PTPN6 mediates the upregulation of THBS1 to promote M2-type macrophage polarization and the progression of renal cancer

PTPN6 mediates the upregulation of THBS1 to promote M2-type macrophage polarization and the progression of renal 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 Article PTPN6 mediates the upregulation of THBS1 to promote M2-type macrophage polarization and the progression of renal cancer Dingkun Hou, Lijuan Kang, Lili Wang, Hongzheng Li, Kaibin Wang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7033454/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 The growing number of renal cancer cases annually underscores the importance of thorough research into its molecular mechanisms to achieve better outcomes. The purpose of this study was to assess how PTPN6 is expressed in various types of renal cancer and its connection to the immune microenvironment, as its role remains uncertain. Preliminary findings revealed that PTPN6 expression is considerably elevated in KIRC relative to normal controls. Elevated PTPN6 levels are also associated with a negative prognosis. A comprehensive review of the differentially expressed genes in KICH, KIRC, and KIRP revealed 55 common regulatory genes associated with immune responses. We hypothesized that PTPN6 plays a role in renal cancer development by regulating immune cell activity. In this study, mouse renal cell carcinoma cell lines with stable PTPN6 knockdown constructed using lentiviral vectors were cocultured with immune cells, and transcriptome sequencing was performed. PTPN6 knockdown significantly reduced THBS1 mRNA expression, as determined by quantitative reverse transcription polymerase chain reaction assay, which subsequently inhibited the M2 macrophage marker CD206+, as determined by flow cytometry. The research results will reveal the mechanism of PTPN6 in renal cell carcinoma and introduce new perspectives on immunotherapy methods Biological sciences/Cancer Biological sciences/Computational biology and bioinformatics Biological sciences/Immunology Health sciences/Oncology PTPN6 THBS1 Macrophage Renal cancer Full Text Additional Declarations No competing interests reported. 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. 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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-7033454","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":498502747,"identity":"25a86068-dd69-492f-a6b2-730d0e30802e","order_by":0,"name":"Dingkun Hou","email":"","orcid":"","institution":"The Second Hospital of Tianjin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Dingkun","middleName":"","lastName":"Hou","suffix":""},{"id":498502748,"identity":"7082ccc3-9262-4c79-813e-ba7fc2227d6e","order_by":1,"name":"Lijuan Kang","email":"","orcid":"","institution":"The Second Hospital of Tianjin Medical 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The purpose of this study was to assess how PTPN6 is expressed in various types of renal cancer and its connection to the immune microenvironment, as its role remains uncertain. Preliminary findings revealed that PTPN6 expression is considerably elevated in KIRC relative to normal controls. Elevated PTPN6 levels are also associated with a negative prognosis. A comprehensive review of the differentially expressed genes in KICH, KIRC, and KIRP revealed 55 common regulatory genes associated with immune responses. We hypothesized that PTPN6 plays a role in renal cancer development by regulating immune cell activity. In this study, mouse renal cell carcinoma cell lines with stable PTPN6 knockdown constructed using lentiviral vectors were cocultured with immune cells, and transcriptome sequencing was performed. PTPN6 knockdown significantly reduced THBS1 mRNA expression, as determined by quantitative reverse transcription polymerase chain reaction assay, which subsequently inhibited the M2 macrophage marker CD206+, as determined by flow cytometry. 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