{"title":"DR1 activates histone gene expression to maintain pancreatic cancer cell survival through the ATAC complex.","authors":"Ziwei Guo, XiangZheng Liu, Mo Chen","doi":"10.1038/s41417-025-00938-0","DOIUrl":null,"url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is the most malignant cancer and is characterized by short survival and limited treatment options. Epigenetic dysregulation is a defining feature of tumorigenesis but remains elusive in PDAC. Here, we identified DR1 as a vulnerability in PDAC. Loss of DR1 inhibited PDAC cell survival through repressing cell cycle. Mechanistically, DR1 recruited the ATAC complex to histone promoter regions to acetylate H3K9 and subsequently activate the expression of histone genes, ultimately promoting cell cycle and maintaining PDAC cell survival. Moreover, we uncovered a positive correlation between histone gene expression and the survival of patients with PDAC. In conclusion, our findings underscore the pivotal role of DR1 in the regulation of histone genes through the ATAC complex, providing a potential therapeutic target for PDAC.</p>","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":" ","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer gene therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41417-025-00938-0","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most malignant cancer and is characterized by short survival and limited treatment options. Epigenetic dysregulation is a defining feature of tumorigenesis but remains elusive in PDAC. Here, we identified DR1 as a vulnerability in PDAC. Loss of DR1 inhibited PDAC cell survival through repressing cell cycle. Mechanistically, DR1 recruited the ATAC complex to histone promoter regions to acetylate H3K9 and subsequently activate the expression of histone genes, ultimately promoting cell cycle and maintaining PDAC cell survival. Moreover, we uncovered a positive correlation between histone gene expression and the survival of patients with PDAC. In conclusion, our findings underscore the pivotal role of DR1 in the regulation of histone genes through the ATAC complex, providing a potential therapeutic target for PDAC.
期刊介绍：
Cancer Gene Therapy is the essential gene and cellular therapy resource for cancer researchers and clinicians, keeping readers up to date with the latest developments in gene and cellular therapies for cancer. The journal publishes original laboratory and clinical research papers, case reports and review articles. Publication topics include RNAi approaches, drug resistance, hematopoietic progenitor cell gene transfer, cancer stem cells, cellular therapies, homologous recombination, ribozyme technology, antisense technology, tumor immunotherapy and tumor suppressors, translational research, cancer therapy, gene delivery systems (viral and non-viral), anti-gene therapy (antisense, siRNA & ribozymes), apoptosis; mechanisms and therapies, vaccine development, immunology and immunotherapy, DNA synthesis and repair.
Cancer Gene Therapy publishes the results of laboratory investigations, preclinical studies, and clinical trials in the field of gene transfer/gene therapy and cellular therapies as applied to cancer research. Types of articles published include original research articles; case reports; brief communications; review articles in the main fields of drug resistance/sensitivity, gene therapy, cellular therapy, tumor suppressor and anti-oncogene therapy, cytokine/tumor immunotherapy, etc.; industry perspectives; and letters to the editor.
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