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Integrative analysis reveals associations between oral microbiota dysbiosis and host genetic and epigenetic aberrations in oral cavity squamous cell carcinoma.
Cai, Liuyang; Zhu, Hengyan; Mou, Qianqian; Wong, Po Yee; Lan, Linlin; Ng, Cherrie W K; Lei, Pu; Cheung, Man Kit; Wang, Daijuanru; Wong, Eddy W Y; Lau, Eric H L; Yeung, Zenon W C; Lai, Ronald; Meehan, Katie; Fung, Sherwood; Chan, Kwan Chee A; Lui, Vivian W Y; Cheng, Alfred S L; Yu, Jun; Chan, Paul K S; Chan, Jason Y K; Chen, Zigui.
Afiliación
  • Cai L; Department of Microbiology, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • Zhu H; Department of Microbiology, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • Mou Q; Department of Microbiology, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • Wong PY; Department of Microbiology, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • Lan L; Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • Ng CWK; Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • Lei P; Department of Microbiology, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • Cheung MK; Department of Microbiology, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • Wang D; Department of Microbiology, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • Wong EWY; Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • Lau EHL; Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • Yeung ZWC; Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • Lai R; Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • Meehan K; Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • Fung S; Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • Chan KCA; Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • Lui VWY; Georgia Cancer Center, Augusta, GA, 30912, USA.
  • Cheng ASL; Department of Medicine, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA.
  • Yu J; School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • Chan PKS; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • Chan JYK; Department of Microbiology, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • Chen Z; Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong, Hong Kong SAR, China. jasonchan@ent.cuhk.edu.hk.
NPJ Biofilms Microbiomes ; 10(1): 39, 2024 Apr 08.
Article en En | MEDLINE | ID: mdl-38589501
ABSTRACT
Dysbiosis of the human oral microbiota has been reported to be associated with oral cavity squamous cell carcinoma (OSCC) while the host-microbiota interactions with respect to the potential impact of pathogenic bacteria on host genomic and epigenomic abnormalities remain poorly studied. In this study, the mucosal bacterial community, host genome-wide transcriptome and DNA CpG methylation were simultaneously profiled in tumors and their adjacent normal tissues of OSCC patients. Significant enrichment in the relative abundance of seven bacteria species (Fusobacterium nucleatum, Treponema medium, Peptostreptococcus stomatis, Gemella morbillorum, Catonella morbi, Peptoanaerobacter yurli and Peptococcus simiae) were observed in OSCC tumor microenvironment. These tumor-enriched bacteria formed 254 positive correlations with 206 up-regulated host genes, mainly involving signaling pathways related to cell adhesion, migration and proliferation. Integrative analysis of bacteria-transcriptome and bacteria-methylation correlations identified at least 20 dysregulated host genes with inverted CpG methylation in their promoter regions associated with enrichment of bacterial pathogens, implying a potential of pathogenic bacteria to regulate gene expression, in part, through epigenetic alterations. An in vitro model further confirmed that Fusobacterium nucleatum might contribute to cellular invasion via crosstalk with E-cadherin/ß-catenin signaling, TNFα/NF-κB pathway and extracellular matrix remodeling by up-regulating SNAI2 gene, a key transcription factor of epithelial-mesenchymal transition (EMT). Our work using multi-omics approaches explored complex host-microbiota interactions and provided important insights into genetic and functional basis in OSCC tumorigenesis, which may serve as a precursor for hypothesis-driven study to better understand the causational relationship of pathogenic bacteria in this deadly cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Boca / Carcinoma de Células Escamosas / Microbiota / Neoplasias de Cabeza y Cuello Límite: Humans Idioma: En Revista: NPJ Biofilms Microbiomes Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Boca / Carcinoma de Células Escamosas / Microbiota / Neoplasias de Cabeza y Cuello Límite: Humans Idioma: En Revista: NPJ Biofilms Microbiomes Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos