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Patients whose ZFP82 promoter CpG island is frequently methylated show non-response, suggesting a role in chemo-resistance. In wild-type p53 cells, ZFP82 recruits HDAC3 to modulate p53 ubiquitin-dependent proteasomal degradation, restoring p53 stability; in mutant p53 cells, ZFP82 regulates HSP70 down-regulation. Restored ZFP82 improves chemosensitivity and suppresses tumorigenicity while correlating with better prognosis, supporting early prediction of responders.",{"@graph":69,"@context":121},[70,84,104],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/zinc-finger-protein-82-regulates-p53-protein-stability-through-histone-deacetylase-and-enhances-neo-adjuvant-chemotherapy-in-esophageal-cancer/376372/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":98,"encodingFormat":97,"isAccessibleForFree":99,"interactionStatistic":100},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/zinc-finger-protein-82-regulates-p53-protein-stability-through-histone-deacetylase-and-enhances-neo-adjuvant-chemotherapy-in-esophageal-cancer/376372.png","ImageObject",300,407,{"name":92,"@type":93},"Anna Hans","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-24",true,{"@type":101,"interactionType":102,"userInteractionCount":14},"InteractionCounter",{"@type":103},"ViewAction",{"@type":105,"mainEntity":106},"FAQPage",[107,113,117],{"name":108,"@type":109,"acceptedAnswer":110},"What link does the study establish between ZFP82 methylation and chemotherapy response?","Question",{"text":111,"@type":112},"Frequent methylation of the ZFP82 promoter CpG island is detected in patients who do not respond to neoadjuvant chemotherapy, indicating an association with esophageal cancer chemo-resistance.","Answer",{"name":114,"@type":109,"acceptedAnswer":115},"How does ZFP82 affect p53 stability in cells expressing wild-type p53?",{"text":116,"@type":112},"ZFP82 binds the HDAC3 promoter and mediates its interaction with p53, leading to HDAC3 cleavage and a reduction in p53 ubiquitin-dependent proteasomal degradation, thereby enhancing wild-type p53 stability.",{"name":118,"@type":109,"acceptedAnswer":119},"How does ZFP82 influence chemosensitivity in esophageal cancer models?",{"text":120,"@type":112},"Restoration of ZFP82 enhances chemosensitivity in esophageal cancer cells with either wild-type or mutant p53 and significantly inhibits in vivo tumorigenicity, with ZFP82 expression correlating with improved prognosis.","https://schema.org",{"og:url":83,"og:type":123,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":125,"canonical":83},"index,follow",{"doc_id":127,"site_id":62},376372,1790243087,{"code":4,"msg":5,"data":130},{"doc_id":127,"user_id":131,"nickname":92,"user_avatar":132,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":138,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},5909892332657,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","[www.nature.com/cddis](www.nature.com/cddis)  \nARTICLE OPEN   \nZinc Finger Protein 82 regulates p53 protein stability through histone deacetylase and enhances neo-adjuvant chemotherapy in esophageal cancer  \nWeiyan Peng1, Hongpeng Wang2, Xuejuan Sun 1, Zhong Xu3, Lingxiang Zhang3 and Lin Ye 3 ✉  \n© The Author(s) 2025  \n|  |  |  |\n| --- | --- | --- |\n|  | Tumor suppressor genes silenced by CpG methylation uncover the molecular mechanism of tumorigenesis and potential tumor biomarkers. Our previous research found that the promoter of zinc-finger protein 82 (ZFP82) was highly methylated in multiple cancers, including esophageal cancer, which induces the occurrence and development of tumors. Here, we describe the frequent detection of methylation of the ZFP82 promoter CpG Island in patients who did not respond to neoadjuvant chemotherapy, indicating that ZFP82 may related to esophageal cancer chemo-resistance. We further verified that in esophageal cancer cells expressing wild-type p53, ZFP82 bound to the HDAC3 promoter and mediated its interaction with p53, leading to HDAC3 cleavage and reduction of p53 ubiquitin-dependent proteasomal degradation, thus enhancing wild-type p53 stability. In cells expressing mutant p53, ZFP82 interacted with HDAC3 to regulate the down-regulation of HSP 70, leading to degradation of mutant p53 . Through both mechanisms, the restoration of ZFP82 enhanced the chemosensitivity in esophageal cancer cells expressing wildtype p53 or mutant p53, significantly inhibiting in vivo tumorigenicity of these cells. Analyses of the expression of ZFP82 and clinical data indicated that ZFP82 expression correlated with improved prognosis. Our results define a mechanism for p53 stabilization via ZFP82-dependent HDAC3 decay under genotoxic stress conditions and validate a candidate bio-marker of early prediction of |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| patients who will respond to esophageal cancer neoadjuvant chemotherapy. |  |  |\n|  | Cell Death and Disease (2025)16:694; [https://doi.org/10.1038/s41419-025-07979-1](https://doi.org/10.1038/s41419-025-07979-1) |  |\n|  |  |  |\n\nINTRODUCTION  \nThe high mortality and low overall survival rates of esophageal cancer highlight the need to improve the treatment response [1, 2] . Neo-adjuvant chemotherapy before surgery is one of the classical therapeutic strategies for late-stage esophageal cancer [3, 4] . However, some patients do not respond to neo-adjuvant chemotherapy, so the overall survival (OS) rate of esophageal cancer remains as low as 15–20% [5, 6] . Understanding the mechanisms of chemotherapy resistance is important to improve the treatment of esophageal cancer.  \nThe chemo-resistance of esophageal cancer involves multiple mechanisms. Aberrant DNA methylation of tumor suppressor genes was recently discovered to be related to the tumorigenesis and chemo-resistance of esophageal cancer [7–10] . Our group has studied the gene methylation profile of esophageal cancer, and determined that Zinc-Finger Protein 82 (ZFP82) was highly methylated in multiple cancers, including esophageal cancer [11] . We also demonstrated that ZFP82 induced apoptosis of esophageal cancer cells [12] . These observations have implicated ZFP82 as a potential therapeutic target for esophageal cancer. Recently, we collected tissue samples from esophageal cancer patients who experienced pathological complete response (pCR)  \nand non-responders (NRs), after neoadjuvant chemotherapy and used the Infinium Methylation EPIC Bead Chip system (Illumina, San Diego, CA, USA) to analyze the DNA methylation profile of the two groups. The findings suggested that ZFP82 was a highly methylated gene in the tissue from NR.  \nPrevious studies have shown that the histone deacetylase complex is the downstream target gene of the zinc finger protein family [13] . Protein structure analysis of histone deacetylase 3 (HDAC3) revea","cbCaiqRmZmQJZyNm","https://ap.wps.com/l/cbCaiqRmZmQJZyNm","pdf",3398708,14,"English","# Introduction\n## Neoadjuvant chemotherapy response challenge in esophageal cancer\n## DNA methylation and ZFP82 as a candidate factor\n## HDAC3 as downstream target within zinc-finger protein pathways","[{\"question\":\"What link does the study establish between ZFP82 methylation and chemotherapy response?\",\"answer\":\"Frequent methylation of the ZFP82 promoter CpG island is detected in patients who do not respond to neoadjuvant chemotherapy, indicating an association with esophageal cancer chemo-resistance.\"},{\"question\":\"How does ZFP82 affect p53 stability in cells expressing wild-type p53?\",\"answer\":\"ZFP82 binds the HDAC3 promoter and mediates its interaction with p53, leading to HDAC3 cleavage and a reduction in p53 ubiquitin-dependent proteasomal degradation, thereby enhancing wild-type p53 stability.\"},{\"question\":\"How does ZFP82 influence chemosensitivity in esophageal cancer models?\",\"answer\":\"Restoration of ZFP82 enhances chemosensitivity in esophageal cancer cells with either wild-type or mutant p53 and significantly inhibits in vivo tumorigenicity, with ZFP82 expression correlating with improved prognosis.\"}]","Zinc Finger Protein 82 regulates p53 protein stability through histone deacetylase and enhances neo-adjuvant chemotherapy in esophageal cancer | PDF",1790218479,35]