LINC01116 binds CPS1 to regulate urea cycle function, thereby promoting progression and chemoresistance in osteosarcoma

LINC01116 binds CPS1 to regulate urea cycle function, thereby promoting progression and chemoresistance in osteosarcoma | 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 LINC01116 binds CPS1 to regulate urea cycle function, thereby promoting progression and chemoresistance in osteosarcoma shiying wu, Hao Zhu, Sen Wang, Yan Zhu, Diankun She, Xi Chen, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9031470/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. The purpose of this study is to explore the regulatory mechanism of LINC01116 in osteosarcoma metastasis and its potential association with the urea cycle and chemoresistance. Transcriptomic profiling was performed, and the results were validated by qRT-PCR in 6 paired osteosarcoma and adjacent non-tumor tissues. Functional assays including in vivo xenograft models were used to verify the effect of LINC01116 on osteosarcoma cell proliferation. RNA-protein interaction studies and ChIRP-MS assays were conducted to confirm the binding between LINC01116 and CPS1.LINC01116 was significantly upregulated in metastatic osteosarcoma lesions. Silencing LINC01116 inhibited osteosarcoma cell proliferation both in vitro and in vivo. Mechanistically, LINC01116 directly binds to CPS1 -the rate-limiting enzyme of the urea cycle, which was confirmed by ChIRP-MS. Perturbing the LINC01116/CPS1 axis reduced citrulline levels, indicating impaired urea cycle function. Additionally, CPS1 silencing enhanced osteosarcoma cell sensitivity to cisplatin. This study identifies a novel LINC01116/CPS1 axis that drives osteosarcoma metastasis by regulating the urea cycle. Targeting this axis can sensitize osteosarcoma to cisplatin treatment, which highlights its potential as a therapeutic target for osteosarcoma. Biological sciences/Cancer Biological sciences/Cell biology Health sciences/Oncology Osteosarcoma LINC01116 CPS1 Urea cycle Chemosensitivity Metastasis Full Text Additional Declarations No competing interests reported. Supplementary Files supplementtable.xlsx supplement.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 18 Mar, 2026 Editor invited by journal 10 Mar, 2026 Editor assigned by journal 09 Mar, 2026 Submission checks completed at journal 06 Mar, 2026 First submitted to journal 06 Mar, 2026 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-9031470","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":608096671,"identity":"105a1d73-e113-4e4f-bee9-7794d2a62236","order_by":0,"name":"shiying wu","email":"","orcid":"","institution":"Nanjing University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"shiying","middleName":"","lastName":"wu","suffix":""},{"id":608096672,"identity":"17b11be5-3678-4767-a11a-f008ca2246ec","order_by":1,"name":"Hao Zhu","email":"","orcid":"","institution":"Chinese Academy of Medical Sciences \u0026 Peking Union Medical 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CPS1, Urea cycle, Chemosensitivity, Metastasis","lastPublishedDoi":"10.21203/rs.3.rs-9031470/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9031470/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eOsteosarcoma is the most common primary malignant bone tumor in children and adolescents. The purpose of this study is to explore the regulatory mechanism of LINC01116 in osteosarcoma metastasis and its potential association with the urea cycle and chemoresistance.\u003c/p\u003e \u003cp\u003eTranscriptomic profiling was performed, and the results were validated by qRT-PCR in 6 paired osteosarcoma and adjacent non-tumor tissues. Functional assays including in vivo xenograft models were used to verify the effect of LINC01116 on osteosarcoma cell proliferation. RNA-protein interaction studies and ChIRP-MS assays were conducted to confirm the binding between LINC01116 and CPS1.LINC01116 was significantly upregulated in metastatic osteosarcoma lesions. Silencing LINC01116 inhibited osteosarcoma cell proliferation both in vitro and in vivo. Mechanistically, LINC01116 directly binds to CPS1 -the rate-limiting enzyme of the urea cycle, which was confirmed by ChIRP-MS. Perturbing the LINC01116/CPS1 axis reduced citrulline levels, indicating impaired urea cycle function. 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