NAR cancer最新文献_第7页

Quantification of radiation-induced DNA double strand break repair foci to evaluate and predict biological responses to ionizing radiation. 量化辐射诱导的DNA双链断裂修复焦点，以评估和预测电离辐射的生物反应。

NAR cancer Pub Date : 2021-10-04 DOI: 10.1093/narcan/zcab046

S. Penninckx, Eloise Pariset, Egle Cekanaviciute, S. Costes

{"title":"Quantification of radiation-induced DNA double strand break repair foci to evaluate and predict biological responses to ionizing radiation.","authors":"S. Penninckx, Eloise Pariset, Egle Cekanaviciute, S. Costes","doi":"10.1093/narcan/zcab046","DOIUrl":"https://doi.org/10.1093/narcan/zcab046","url":null,"abstract":"Radiation-induced foci (RIF) are nuclear puncta visualized by immunostaining of proteins that regulate DNA double-strand break (DSB) repair after exposure to ionizing radiation. RIF are a standard metric for measuring DSB formation and repair in clinical, environmental and space radiobiology. The time course and dose dependence of their formation has great potential to predict in vivo responses to ionizing radiation, predisposition to cancer and probability of adverse reactions to radiotherapy. However, increasing complexity of experimentally and therapeutically setups (charged particle, FLASH …) is associated with several confounding factors that must be taken into account when interpreting RIF values. In this review, we discuss the spatiotemporal characteristics of RIF development after irradiation, addressing the common confounding factors, including cell proliferation and foci merging. We also describe the relevant endpoints and mathematical models that enable accurate biological interpretation of RIF formation and resolution. Finally, we discuss the use of RIF as a biomarker for quantification and prediction of in vivo radiation responses, including important caveats relating to the choice of the biological endpoint and the detection method. This review intends to help scientific community design radiobiology experiments using RIF as a key metric and to provide suggestions for their biological interpretation.","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":"3 4 1","pages":"zcab046"},"PeriodicalIF":0.0,"publicationDate":"2021-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46362143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

Epigenetic alterations at distal enhancers are linked to proliferation in human breast cancer 远端增强子的表观遗传改变与人类乳腺癌的增殖有关

NAR cancer Pub Date : 2021-04-14 DOI: 10.1093/narcan/zcac008

Jørgen Ankill, M. R. Aure, Sunniva Bjørklund, Severin R. E. Langberg, V. Kristensen, V. Vitelli, X. Tekpli, Thomas Fleischer

{"title":"Epigenetic alterations at distal enhancers are linked to proliferation in human breast cancer","authors":"Jørgen Ankill, M. R. Aure, Sunniva Bjørklund, Severin R. E. Langberg, V. Kristensen, V. Vitelli, X. Tekpli, Thomas Fleischer","doi":"10.1093/narcan/zcac008","DOIUrl":"https://doi.org/10.1093/narcan/zcac008","url":null,"abstract":"Breast cancer is a highly heterogeneous disease driven by multiple factors including genetic and epigenetic alterations. DNA methylation patterns have been shown to be altered on a genome-wide scale and previous studies have highlighted the critical role of aberrant DNA methylation on gene expression and breast cancer pathogenesis. Here, we perform genome-wide expression-methylation Quantitative Trait Loci (emQTL), a method for integration of CpG methylation and gene expression to identify disease-driving genes under epigenetic control. By grouping these emQTLs by biclustering we identify associations representing important biological processes associated with breast cancer pathogenesis such as proliferation and tumor infiltrating fibroblasts. We report hypomethylation at enhancers carrying transcription factor binding sites of key proliferation-driving transcription factors such as CEBP-β, FOSL1, and FOSL2, with concomitant high expression of cell cycle- and proliferation-related genes in aggressive breast tumors. The identified CpGs and genes were found to be connected through chromatin loops, together indicating that proliferation in aggressive breast tumors is under epigenetic regulation by DNA methylation. Interestingly, there was a significant correlation between proliferation-related DNA methylation and gene expression also within subtypes of breast cancer, thereby showing that varying proliferation may be explained by epigenetic profiles across breast cancer subtypes. Indeed, the identified proliferation gene signature was prognostic both in the Luminal A and Luminal B subtypes. Taken together, we show that proliferation in breast cancer is linked to hypomethylation at specific enhancers and transcription factor binding mediated through chromatin loops.","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43383208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Integrative genome-wide analysis reveals EIF3A as a key downstream regulator of translational repressor protein Musashi 2 (MSI2) 全基因组综合分析显示EIF3A是翻译抑制蛋白Musashi 2（MSI2）的关键下游调节因子

NAR cancer Pub Date : 2021-02-07 DOI: 10.1093/narcan/zcac015

Shilpita Karmakar, Oscar Ramirez, Kiran V. Paul, A. Gupta, Valentina Botti, Igor Ruiz de los Mozos, Nils Neuenkirchen, R. J. Ross, K. Neugebauer, Manoj M. Pillai

{"title":"Integrative genome-wide analysis reveals EIF3A as a key downstream regulator of translational repressor protein Musashi 2 (MSI2)","authors":"Shilpita Karmakar, Oscar Ramirez, Kiran V. Paul, A. Gupta, Valentina Botti, Igor Ruiz de los Mozos, Nils Neuenkirchen, R. J. Ross, K. Neugebauer, Manoj M. Pillai","doi":"10.1093/narcan/zcac015","DOIUrl":"https://doi.org/10.1093/narcan/zcac015","url":null,"abstract":"Musashi 2 (MSI2) is an RNA binding protein (RBP) that regulates asymmetric cell division and cell fate decisions in normal and cancer stem cells. MSI2 appears to repress translation by binding to 3’ untranslated regions (3’UTRs) of mRNA, but the identity of functional targets remains unknown. Here we used iCLIP to identify direct RNA binding partners of MSI2 and integrated these data with polysome profiling to obtain insights into MSI2 function. iCLIP revealed specific MSI2 binding to thousands of target mRNAs largely in 3’UTRs, but translational differences were restricted to a small fraction of these transcripts, indicating that MSI2 regulation is not triggered by simple binding. Instead, the functional targets identified here were bound at higher density and contain more “U/TAG” motifs compared to targets bound non-productively. To further distinguish direct and indirect targets, MSI2 was acutely depleted. Surprisingly, only 50 transcripts were found to undergo translational induction on acute MSI2 loss. Eukaryotic elongation factor 3A (EIF3A) was determined to be an immediate, direct target. We propose that MSI2 down-regulation of EIF3A amplifies these effects on the proteome. Our results also underscore the challenges in defining functional targets of RBP since mere binding does not imply a discernible functional interaction.","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47690977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Androgen signaling connects short isoform production to breakpoint formation at Ewing sarcoma breakpoint region 1 雄激素信号传导将尤因肉瘤断点区1的短亚型产生与断点形成联系起来

NAR cancer Pub Date : 2020-03-26 DOI: 10.1101/2020.03.25.008391

T. R. Nicholas, Peter C. Hollenhorst

引用次数: 1