Zinc Finger Protein ZFP82 regulates p53 protein stability through histone deacetylase 3 and enhances neo-adjuvant chemotherapy in esophageal cancer

Zinc Finger Protein ZFP82 regulates p53 protein stability through histone deacetylase 3 and enhances neo-adjuvant chemotherapy in esophageal 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 Zinc Finger Protein ZFP82 regulates p53 protein stability through histone deacetylase 3 and enhances neo-adjuvant chemotherapy in esophageal cancer lin ye, Weiyan Peng, Hongpeng Wang, Xuejuan Sun, Lingxiang Zhang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4845430/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 We previous revealed Zinc-Finger Protein 82 (ZFP82) was highly methylated in multiple cancers, including esophageal cancer. Here we show that ZFP82 is highly methylated in patients who experienced non-responders in Neoadjuvant chemotherapy compared to those who are pathological complete response by Infinium Methylation EPIC Bead Chip. The inhibition of p53 activity by histone deacetylase 3 (HDAC3) has been reported, but the precise molecular mechanism is unknown. We verified here that ZFP82 bound to HDAC3 promoter and mediated its interaction with p53, which induced HDAC3 cleavage and ubiquitin-dependent proteasomal degradation. Ectopic ZFP82 induced p53 stabilization and HDAC3 cleavage, indicating an essential role of ZFP82 in p53 activation. Restoration of ZFP82 restored the chemo-sensitivity in esophageal cancer cell both expressing wild type p53 and mutant p53, significantly inhibited in vivo tumorigenicity of esophageal cells and correlated with better prognosis in patients. Our results define a mechanism for p53 stabilization via ZFP82-dependent HDAC3 decay under genotoxic stress conditions and validated a candidate bio-marker of early prediction of patients responds to esophageal cancer Neoadjuvant chemotherapy. Biological sciences/Cancer/Tumour biomarkers Biological sciences/Cancer/Cancer therapy/Cancer therapeutic resistance Full Text Additional Declarations (Not answered) Tables 1 and 2 are available in the Supplementary Files section. Supplementary Files WB.pdf table.pdf 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-4845430","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":337377005,"identity":"dcbe4360-eac1-4485-a2ff-03ccf8dee21d","order_by":0,"name":"lin 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Here we show that ZFP82 is highly methylated in patients who experienced non-responders in Neoadjuvant chemotherapy compared to those who are pathological complete response by Infinium Methylation EPIC Bead Chip. The inhibition of p53 activity by histone deacetylase 3 (HDAC3) has been reported, but the precise molecular mechanism is unknown. We verified here that ZFP82 bound to HDAC3 promoter and mediated its interaction with p53, which induced HDAC3 cleavage and ubiquitin-dependent proteasomal degradation. Ectopic ZFP82 induced p53 stabilization and HDAC3 cleavage, indicating an essential role of ZFP82 in p53 activation. Restoration of ZFP82 restored the chemo-sensitivity in esophageal cancer cell both expressing wild type p53 and mutant p53, significantly inhibited in vivo tumorigenicity of esophageal cells and correlated with better prognosis in patients. 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