Association of Porphyromonas gingivalis-infected oral squamous cell carcinoma cell-secreted exosomal miR-3648-1-p5 with tumor progression

Oral squamous cell carcinoma accounts for over 90% of oral malignancies and remains a major global public health concern. Our previous study identified Porphyromonas gingivalis (P. gingivalis) as a key microbial factor in oral squamous cell carcinoma initiation and progression. However, the precise mechanisms by which P. gingivalis infection contributes to tumor progression remain unclear. Pathogens regulate exosome secretion during bacterial infection; therefore, this study aimed to investigate the role of exosomes from P. gingivalis-infected oral squamous cell carcinoma cells (Pg.Ex) in tumor progression. We isolated exosomes using differential centrifugation. To elucidate the mechanisms by which Pg.Ex promote oral squamous cell carcinoma progression, microRNA sequencing was performed on exosomes isolated from P. gingivalis-infected and uninfected cells. Furthermore, the biological roles of Pg.Ex and exosomal miR-3648-1-p5 in oral squamous cell carcinoma tumor growth were examined in vitro and in vivo. We found that P. gingivalis-infected oral squamous cell carcinoma cells released lower concentrations and larger particle sizes of exosomes. Pg.Ex had lower levels of miR-3648-1-p5 and could be transferred to uninfected cells to promote the malignant phenotype of oral squamous cell carcinoma cells, in vitro and in vivo. These findings reveal an unknown connection between low exosomal miR-3648-1-p5 expression in P. gingivalis-infected oral squamous cell carcinoma cells and oral squamous cell carcinoma progression. Therefore, targeting Pg.Ex and miR-3648-1-p5 may present a promising therapeutic strategy for the treatment of oral squamous cell carcinoma.