Introduction/Background Human papillomavirus type 16 (HPV16) is a central carcinogenic factor in cervical cancer.VAMP8 (vesicle-associated membrane protein 8) is a membrane-bound protein involved in intracellular vesicle transport and fusion processes, regulating various biological activities. This study aims to investigate the expression and biological function of VAMP8 in cervical disease progression.

Methodology Proteomics analysis was employed to study the relative expression of VAMP8 in cervical cell lines (ECT-1, Hela, SiHa, C-33). TCGA was used to explore the cancer prognosis and immune infiltration.CCK-8, Transwell, and flow cytometry techniques were employed to analyze the effects of VAMP8 on cell proliferation, migration, invasion,cell cycle distribution, and apoptosis. Transmission electron microscopy, immunofluorescence, and WB experiments were conducted to detect autophagy levels. Tumor growth and metastasis in vivo was evaluated using a nude mouse subcutaneous xenograft model.

Results Proteomics analysis revealed that VAMP8 expression was higher in LSIL than HSIL and cervical cancer but significantly higher than in normal HPV16-negative cervical tissues. In vitro experiments demonstrated that relative overexpression of VAMP8 in HPV16-positive ECT-1 cells resulted in increased autophagic flux, decreased cell proliferation, migration, invasion, increased apoptosis, and an increased proportion of cells in the G1 phase. In other words, elevated VAMP8 expression in HPV16-infected cervical cells promotes autophagy while inhibiting normal cervical cell growth. In cervical cancer cells, high VAMP8 expression promotes autophagy and tumor cell growth. In vivo experiments further confirmed that overexpression of VAMP8 promotes cervical cancer growth and metastasis.

Conclusion VAMP8 promotes autophagy in cervical cells, inhibiting cellular function and maintaining homeostasis in the early stages of persistent HPV16 infection. However, in cervical cancer, VAMP8 promotes tumor cell growth and metastasis. This may be due to the differing roles of autophagy at various stages of tumor development. These findings suggest that VAMP8 may serve as a potential prognostic biomarker and therapeutic target for cervical cancer.

Disclosures The work was supported by National Natural Science Foundation of China (No. 82001500).