HOXA5 Inhibits Malignant Progression of Lung Adenocarcinoma via Neutrophil Extracellular Traps

HOXA5 Inhibits Malignant Progression of Lung Adenocarcinoma via Neutrophil Extracellular Traps | 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 HOXA5 Inhibits Malignant Progression of Lung Adenocarcinoma via Neutrophil Extracellular Traps Lijuan Ye, Kaimin Xu, Chenyang Zhan, Liqiong Wang, Baolong Jia This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9391532/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 The biological function, diagnostic and prognostic significance of HOXA5 in lung adenocarcinoma (LUAD), as well as its molecular mechanism in regulating neutrophil extracellular trap (NET) formation, remain incompletely understood. In this study, integrated analysis of TCGA data and immunohistochemistry (IHC) revealed significantly reduced HOXA5 expression in LUAD tissues compared to adjacent normal tissues. Notably, lower HOXA5 levels were associated with male gender, bone metastasis, and advanced TNM stage. Survival analysis demonstrated that elevated HOXA5 expression correlated with improved prognosis in LUAD patients, however, Cox regression indicated that HOXA5 was not an independent prognostic factor for overall survival. Western blotting identified H1734 cells as having the lowest and H1299 cells the highest endogenous HOXA5 expression. Functional assays demonstrated that HOXA5 overexpression suppressed proliferation, migration, and invasion in A549, H1734, and H1299 cells, while HOXA5 knockdown exerted opposing oncogenic effects. Mechanistically, ELISA analysis revealed that HOXA5 overexpression reduced myeloperoxidase (MPO) levels, thereby inhibiting NET formation, whereas HOXA5 silencing enhanced MPO expression and promoted NET generation. Furthermore, NETs were found to exacerbate LUAD cell malignancy, an effect that was attenuated by HOXA5 upregulation. In summary, our findings establish HOXA5 as a tumor-suppressive factor in LUAD, with reduced expression linked to aggressive clinicopathological features and poor prognosis. HOXA5 exerts its anti-tumor effects by suppressing NET formation, thereby inhibiting LUAD progression. This study elucidates the regulatory role of the HOXA5-NET axis in LUAD pathogenesis, offering novel insights for potential diagnostic and therapeutic strategies. Biological sciences/Cancer Health sciences/Oncology Lung adenocarcinoma HOXA5 Neutrophil extracellular traps NETs Malignant progression Full Text Additional Declarations No competing interests reported. Supplementary Files a1.pdf a2.pdf c2.pdf c1.pdf Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 30 Apr, 2026 Editor assigned by journal 30 Apr, 2026 Editor invited by journal 30 Apr, 2026 Submission checks completed at journal 19 Apr, 2026 First submitted to journal 19 Apr, 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-9391532","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":634442785,"identity":"2e758eff-cb61-4c6b-a30c-d77aa3c91a48","order_by":0,"name":"Lijuan 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Neutrophil extracellular traps, NETs, Malignant progression","lastPublishedDoi":"10.21203/rs.3.rs-9391532/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9391532/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe biological function, diagnostic and prognostic significance of HOXA5 in lung adenocarcinoma (LUAD), as well as its molecular mechanism in regulating neutrophil extracellular trap (NET) formation, remain incompletely understood. 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