HPV16 E6 promotes cell proliferation, migration, and invasion of human cervical cancer cells by elevating both EMT and stemness characteristics.

Abstract

In most cases of cervical cancer, the high risk of the disease is caused by the human papilloma virus (HPV). Surgery or radiation usually benefits patients with early cervical cancer, while the metastatic one is uncurable and new therapeutic strategies and approaches are required. In this study, HPV16 E6 silence or overexpression were carried out to evaluate the possible mechanisms of HPV16 E6 function in cervical cancer cells with different HPV16 E6 expression background. HPV16 E6-positive cervical cancer cell Siha exerts significantly stronger cell invasion and migration potentials than the HPV16 E6-negative C33A cells. HPV16 E6 silence significantly weakened the potentials of cell invasion and migration, cell proliferation and stemness characteristic in Siha cells. Meanwhile, the overexpression of HPV16 E6 effectively promoted the cell proliferation and stemness characteristic in C33A cells. Our data also indicated a positive association between HPV16 E6 and the levels of epithelial to mesenchymal transition (EMT), and cell stemness. The ectopic expression of OCT4 could effectively reverse the inhibitory roles of HPV16 E6 silence on cell migration, invasion, and stemness in Siha cells. More interestingly, we found that HPV16 E6 might promote the OCT4 expression by impairing the direct binding of p53 on the promoter and activate its transcription. Taken together, our results indicated that HPV16 E6 could promoted the potential cell proliferation, migration, and invasion of human cervical cancer cells by modulating EMT and cell stemness. Our data provide a novel mechanism for how HPV16 E6 acts as a key risk factor for cervical cancer development and progression.