HPV11E6/E7 induces nasal epithelial hyperplasia through JAK2/STAT3 signaling pathway.

Objectives: Nasal mucosal epithelial hyperplasia can cause nasal hyperplastic diseases, more studies have confirmed that different subtypes of HPV infection play a significant role in nasal proliferative diseases, especially nasal inverted papilloma (NIP). This study aims to elucidate the role and mechanism of the HPV11 subtype in regulating nasal epithelial hyperplasia.

Methods: In our previous study, the expression of HPV infection in NIP was analyzed by Flow-through hybridization and gene chip (HybridMax), with the highest expression rate observed for the HPV11 subtype. Therefore, we aimed to overexpress HPV11E6/E7 in nasal mucosal epithelial cells (HNEpC) to verify the regulatory role and mechanism of HPV11 in nasal epithelial hyperplasia at the cellular level. In this manuscript, we constructed a lentiviral vector overexpressing HPV11E6/E7 and transfected it into HNEpC. We used HNEpC as the control group and HPV11E6/E7-overexpressing cells as the experimental group. Cell proliferation was assessed using CCK-8, EdU, and colony formation assays. Cell migration ability was evaluated by wound healing and Transwell assays. Protein expression levels related to apoptosis, epithelial-mesenchymal transition (EMT), and the JAK2/STAT3 pathway were analyzed by western blot.

Results: The results showed that overexpression of HPV11E6/E7 significantly increased the proliferation and migration of nasal epithelial cells, promoted the progression of EMT, and inhibited cell apoptosis. Further verification showed that the overexpression of HPV11E6/E7 significantly promoted the activation of the JAK2/STAT3 signaling pathway.

Conclusions: In summary, we found that low-risk subtype HPV11 promotes nasal mucosal epithelial hyperplasia and malignant progression by increasing activation of the JAK2/STAT3 pathway. The JAK2/STAT3 pathway has been prioritized due to its established role in promoting cell proliferation and EMT in HPV-related diseases.