Ageing and cancer research & treatment最新文献

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DNA methylation landscapes in human cells and their chromatin determinants. 人类细胞中的DNA甲基化景观及其染色质决定因素。
Ageing and cancer research & treatment Pub Date : 2026-01-01 Epub Date: 2025-12-18 DOI: 10.70401/acrt.2025.0007
Wei Cui, Zhijun Huang, Gerd P Pfeifer
{"title":"DNA methylation landscapes in human cells and their chromatin determinants.","authors":"Wei Cui, Zhijun Huang, Gerd P Pfeifer","doi":"10.70401/acrt.2025.0007","DOIUrl":"10.70401/acrt.2025.0007","url":null,"abstract":"<p><strong>Background: </strong>DNA methylation patterns are established during development and are propagated in a cell type specific manner, but these patterns may become aberrant during aging and cancer. Regions of alternating high and moderate to low levels of DNA methylation exist along all chromosomes in human cells. It is unclear how these distinct DNA methylation blocks are established. Most of the prior work in this area has been performed with mouse embryonic stem cells.</p><p><strong>Methods: </strong>Using whole genome bisulfite sequencing and chromatin-immunoprecipitation sequencing, we have profiled DNA methylation at single base resolution and various histone modifications in human bronchial epithelial cells.</p><p><strong>Results: </strong>We found that many regions of lower DNA methylation (< 50%) are characterized by presence of the Polycomb repressive complex 2 (PRC2) mark, histone H3K27 trimethylation, but less so by the PRC1 mark histone H2AK119 monoubiquitylation. These same PRC2-marked regions also showed a depletion of histone H3K36 di- and tri-methylation.</p><p><strong>Conclusion: </strong>Since H3K36me2 and H3K36me3 are recognized by the reader domains of the DNA methyltransferases DNMT3A and DNMT3B, and H3K36 methylation is a block to the PRC2 methyltransferases, these two types of crosstalk may explain the stable maintenance and antagonism between H3K27me3 and broad DNA methylation domains. However, methylated CpG islands are depleted of H3K36me2 and show a different relationship between DNA methylation and H3K36me2 deposition compared to non-CpG island regions. The data give insight into how DNA methylation patterns are established in human cells. We discuss these findings and their potential relevance for altered DNA methylation patterns seen in aging tissues and in cancer cells.</p>","PeriodicalId":521202,"journal":{"name":"Ageing and cancer research & treatment","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12865891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146121713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
KCTD10 as a selective cancer dependency from transcription-replication conflicts (TRCs). 转录-复制冲突(TRCs)对KCTD10的选择性癌症依赖性
Ageing and cancer research & treatment Pub Date : 2026-01-01 Epub Date: 2026-03-04 DOI: 10.70401/acrt.2026.0015
Jake A Kloeber, Bin Chen, Robert Mutter, Jinzhou Huang, Zhenkun Lou
{"title":"KCTD10 as a selective cancer dependency from transcription-replication conflicts (TRCs).","authors":"Jake A Kloeber, Bin Chen, Robert Mutter, Jinzhou Huang, Zhenkun Lou","doi":"10.70401/acrt.2026.0015","DOIUrl":"10.70401/acrt.2026.0015","url":null,"abstract":"<p><p>Transcription-replication conflicts (TRCs) are an increasingly recognized driver of genome instability in human cells. We recently identified the CUL3 adaptor KCTD10 as a sensor of co-directional TRCs, recruiting CUL3 to ubiquitinate transcriptional machinery and clear the path for replication forks. Here, we discuss the implications of this conflict-resolution pathway for human cancer. By integrating our mechanistic findings with large-scale functional genomics datasets, we identify oncogenic conditions that potentially create TRC-rich environments and render cells selectively dependent on KCTD10. These contexts reveal new mechanistic insights and potential therapeutic opportunities across a range of human cancers.</p>","PeriodicalId":521202,"journal":{"name":"Ageing and cancer research & treatment","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147795592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immunotherapy: should we worry about immunosenescence? 免疫治疗:我们应该担心免疫衰老吗?
Ageing and cancer research & treatment Pub Date : 2024-04-22 DOI: 10.70401/acrt.2024.104
Asli Özkan, Nienke A de Glas, Johanneke E A Portielje
{"title":"Immunotherapy: should we worry about immunosenescence?","authors":"Asli Özkan, Nienke A de Glas, Johanneke E A Portielje","doi":"10.70401/acrt.2024.104","DOIUrl":"10.70401/acrt.2024.104","url":null,"abstract":"<p><p>The global aging population is expected to experience a nofigure increase in cancer incidence, particularly among individuals aged 70 and older. At the same time, the extensive use of immune checkpoint inhibitors (ICIs) in cancer treatment raises questions about the influence of immunosenescence, the age-related decline in immune function, on treatment efficacy in older patients. Despite promising outcomes, resistance to immunotherapies and the occurrence of severe immune-related adverse events (irAEs) remain challenges. Limited research has explored the correlation between immunosenescence markers in peripheral blood and the tumour microenvironment (TME), frailty, and ICI response, and irAEs in older patients. This commentary explores the interrelationship between immunosenescence and immunotherapy in older and frail patients with cancer undergoing ICI therapy. Understanding the impact of immunosenescence on treatment response and irAEs, and identifying reliable biomarkers, is crucial for future research in geriatric oncology, as this will possibly facilitate patient stratification and personalized treatment approaches, ultimately improving patient outcomes while minimizing irAE-related risks.</p>","PeriodicalId":521202,"journal":{"name":"Ageing and cancer research & treatment","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7618642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146000398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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