Wenye Xu, Yuchen Zhang, Dongjiao Chen, Dan Huang, Yang Zhao, Wei Hu, Ling Lin, Yingzhi Liu, Shilan Wang, Judeng Zeng, Chuan Xie, Hung Chan, Qing Li, Huarong Chen, Xiaodong Liu, Sunny H Wong, Jun Yu, Francis K L Chan, Matthew T V Chan, Siew C Ng, William K K Wu, Lin Zhang
{"title":"阐明核酸镰刀菌分泌的诱变剂在大肠癌致癌过程中的基因毒性","authors":"Wenye Xu, Yuchen Zhang, Dongjiao Chen, Dan Huang, Yang Zhao, Wei Hu, Ling Lin, Yingzhi Liu, Shilan Wang, Judeng Zeng, Chuan Xie, Hung Chan, Qing Li, Huarong Chen, Xiaodong Liu, Sunny H Wong, Jun Yu, Francis K L Chan, Matthew T V Chan, Siew C Ng, William K K Wu, Lin Zhang","doi":"10.1186/s13099-024-00640-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Fusobacterium nucleatum (F. nucleatum) is one of the key tumorigenic bacteria in colorectal cancer (CRC), yet how F. nucleatum is involved in colorectal cancer carcinogenesis remains unknown.</p><p><strong>Results: </strong>In the present study, we carried out PathSeq analysis on RNA sequencing data from the 430 primary colon adenocarcinomas in TCGA database to assess the relationship between patients' survival and F. nucleatum abundance. Among patients with cecum and ascending colon tumors, we found that F. nucleatum transcriptome abundance is positively correlated with mutation load. We further demonstrated that patients with both high tumoral abundance of F. nucleatum and high mutation load exhibited poorer survival and DNA damage. We furthermore determined that F. nucleatum-conditioned medium (Fn. CM) induces DNA damage in both in vitro and in vivo studies. In addition, two F. nucleatum-secreted mutagens, namely DL-homocystine and allantoic acid, were identified to lead to DNA damage.</p><p><strong>Conclusions: </strong>Our finding delineates the genotoxicity of F.nucleatum-secreted mutagens, which provides a basis for further work to investigate the role of F. nucleatum in the pathogenicity of CRC.</p>","PeriodicalId":12833,"journal":{"name":"Gut Pathogens","volume":"16 1","pages":"50"},"PeriodicalIF":4.3000,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438217/pdf/","citationCount":"0","resultStr":"{\"title\":\"Elucidating the genotoxicity of Fusobacterium nucleatum-secreted mutagens in colorectal cancer carcinogenesis.\",\"authors\":\"Wenye Xu, Yuchen Zhang, Dongjiao Chen, Dan Huang, Yang Zhao, Wei Hu, Ling Lin, Yingzhi Liu, Shilan Wang, Judeng Zeng, Chuan Xie, Hung Chan, Qing Li, Huarong Chen, Xiaodong Liu, Sunny H Wong, Jun Yu, Francis K L Chan, Matthew T V Chan, Siew C Ng, William K K Wu, Lin Zhang\",\"doi\":\"10.1186/s13099-024-00640-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Fusobacterium nucleatum (F. nucleatum) is one of the key tumorigenic bacteria in colorectal cancer (CRC), yet how F. nucleatum is involved in colorectal cancer carcinogenesis remains unknown.</p><p><strong>Results: </strong>In the present study, we carried out PathSeq analysis on RNA sequencing data from the 430 primary colon adenocarcinomas in TCGA database to assess the relationship between patients' survival and F. nucleatum abundance. Among patients with cecum and ascending colon tumors, we found that F. nucleatum transcriptome abundance is positively correlated with mutation load. We further demonstrated that patients with both high tumoral abundance of F. nucleatum and high mutation load exhibited poorer survival and DNA damage. We furthermore determined that F. nucleatum-conditioned medium (Fn. CM) induces DNA damage in both in vitro and in vivo studies. In addition, two F. nucleatum-secreted mutagens, namely DL-homocystine and allantoic acid, were identified to lead to DNA damage.</p><p><strong>Conclusions: </strong>Our finding delineates the genotoxicity of F.nucleatum-secreted mutagens, which provides a basis for further work to investigate the role of F. nucleatum in the pathogenicity of CRC.</p>\",\"PeriodicalId\":12833,\"journal\":{\"name\":\"Gut Pathogens\",\"volume\":\"16 1\",\"pages\":\"50\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-09-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438217/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Gut Pathogens\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13099-024-00640-w\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gut Pathogens","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13099-024-00640-w","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Elucidating the genotoxicity of Fusobacterium nucleatum-secreted mutagens in colorectal cancer carcinogenesis.
Background: Fusobacterium nucleatum (F. nucleatum) is one of the key tumorigenic bacteria in colorectal cancer (CRC), yet how F. nucleatum is involved in colorectal cancer carcinogenesis remains unknown.
Results: In the present study, we carried out PathSeq analysis on RNA sequencing data from the 430 primary colon adenocarcinomas in TCGA database to assess the relationship between patients' survival and F. nucleatum abundance. Among patients with cecum and ascending colon tumors, we found that F. nucleatum transcriptome abundance is positively correlated with mutation load. We further demonstrated that patients with both high tumoral abundance of F. nucleatum and high mutation load exhibited poorer survival and DNA damage. We furthermore determined that F. nucleatum-conditioned medium (Fn. CM) induces DNA damage in both in vitro and in vivo studies. In addition, two F. nucleatum-secreted mutagens, namely DL-homocystine and allantoic acid, were identified to lead to DNA damage.
Conclusions: Our finding delineates the genotoxicity of F.nucleatum-secreted mutagens, which provides a basis for further work to investigate the role of F. nucleatum in the pathogenicity of CRC.
Gut PathogensGASTROENTEROLOGY & HEPATOLOGY-MICROBIOLOGY
CiteScore
7.70
自引率
2.40%
发文量
43
期刊介绍：
Gut Pathogens is a fast publishing, inclusive and prominent international journal which recognizes the need for a publishing platform uniquely tailored to reflect the full breadth of research in the biology and medicine of pathogens, commensals and functional microbiota of the gut. The journal publishes basic, clinical and cutting-edge research on all aspects of the above mentioned organisms including probiotic bacteria and yeasts and their products. The scope also covers the related ecology, molecular genetics, physiology and epidemiology of these microbes. The journal actively invites timely reports on the novel aspects of genomics, metagenomics, microbiota profiling and systems biology.
Gut Pathogens will also consider, at the discretion of the editors, descriptive studies identifying a new genome sequence of a gut microbe or a series of related microbes (such as those obtained from new hosts, niches, settings, outbreaks and epidemics) and those obtained from single or multiple hosts at one or different time points (chronological evolution).
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