Transcriptome Analysis of HNSCC by Aggregatibacter actinomycetemcomitans Extracellular Vesicles

ABSTRACT Objectives The role of extracellular vesicles (EVs), also known as outer membrane vesicles (OMVs), secreted by oral bacteria in the progression of head and neck squamous cell carcinomas (HNSCCs), is largely unexplored. This study aimed to investigate the influence of bacterial EVs, specifically those derived from Aggregatibacter actinomycetemcomitans ( Aa ), on the progression of HNSCC. Materials and Methods FaDu and UMSCC1 cell lines were treated with Aa ‐derived EVs, and oncogenic activities were assessed. Comprehensive cellular and RNA‐sequencing transcriptome analyses were conducted to assess the impact of these EVs on cell cycle progression and gene expression. Results Our findings reveal that Aa ‐derived EVs accelerate cell cycle progression through the S and G2 phases and enhance invasion in HNSCC cell lines. RNA‐sequencing analysis showed that Aa ‐derived EVs exert a more significant effect on general transcript expression than on microRNA profiles, except for miR‐146a, which is recognized as a key factor in both carcinogenesis and immune modulation. Conclusions Bacterial EVs, particularly from periodontal pathogens like Aa , are significant modulators within the oral cancer environment, potentially affecting cellular behavior and gene expression profiles. This study highlights the complex relationship between periodontal health and oral carcinogenesis, emphasizing the significant role of bacterial EVs in HNSCC progression.