VAMP7-mediated autophagy regulates cervical cancer progression associated with persistent HPV16 infection.

BACKGROUD: Persistent infection with high-risk human papillomavirus type 16 (HPV16) is a principal etiological factor in cervical cancer. Nevertheless, the molecular events linking HPV16-associated lesion progression to malignant transformation remain insufficiently characterized, particularly those involving vesicular trafficking and autophagy regulation.

METHODS

Proteomic analysis was conducted across five stages of HPV16-associated cervical lesion progression to identify differentially expressed proteins. The expression of vesicle-associated membrane protein 7 (VAMP7) was validated in cervical tissue specimens and cellular models. Gain- and loss-of-function approaches were employed to assess the effects of VAMP7 on cellular proliferation, migration, invasion, and apoptosis. Autophagic activity was evaluated by LC3 lipidation, autophagosome accumulation, and analysis of SNARE complexrelated proteins. The in vivo effects of VAMP7 were examined using xenograft tumor models.

RESULTS

VAMP7 demonstrated dynamic expression changes during cervical lesion progression, characterized by decreased expression in HPV16-positive non-malignant tissues and a gradual increase with disease severity, reaching the highest levels in advanced cervical cancer. Functionally, VAMP7 enhanced proliferation, migration, and invasion while inhibiting apoptosis in cervical cancer cells, whereas distinct effects were observed in non-tumor cervical epithelial cells. Mechanistically, VAMP7 regulated autophagic flux through modulation of SNARE-mediated vesicle fusion, resulting in altered autophagosome accumulation and autophagy-related signaling. In xenograft models, VAMP7 overexpression significantly promoted tumor growth and increased the expression of autophagy-associated markers.

CONCLUSION

These data indicate that dysregulation of VAMP7-mediated autophagy contributes to cervical carcinogenesis in an HPV16-associated context. VAMP7 may represent a potential therapeutic target for the treatment of cervical cancer.

KEY POINTS: VAMP7 displays dynamic expression changes during HPV16-associated cervical lesion progression. VAMP7 promotes malignant phenotypes of cervical cancer cells by regulating autophagic flux via SNARE-mediated vesicle fusion. Dysregulated VAMP7-mediated autophagy contributes to cervical carcinogenesis in an HPV16-associated context.