Human Papillomavirus16 E6 Contributes To Cell Carcinogenesis By Upregulating Aurora A Expression

Background: Over-expression of Aurora A kinase happens in some types of cancer,thus results in chromosome instability and phosphorylation-mediated ubiquitylation and degradation of p53 for tumorigenesis.High-risk HPV16E6 leads to cell immortality and behavioral transformation through interaction with a number of cellular factors.Our previous work has demonstrated that HPV16E6 combines with Aurora A and enhances Aurora A expression.On this basis,we further studied its biological significance.Methods: HPV16 E6 and/or Aurora A were transfected into HEK 293 cells,p53 expression was detected by protein degradation experiments to detect the effect of Aurora A on HPV E6 induced p53 degradation.Different combination groups of p53,HPV16E6 and /or Aurora A were transfected into Saos2 cells,then flow cytometry and colony formation analysis were used to detect the effect on p53 induced apoptosis.Aurora A expression in Caski cells was knocked down by lentivirus-mediated shRNA against Aurora A,thenthe effect of Aurora A on tumorigenesis of cervical cancer cells was verified by nude mouse tumor xenograft.Results: The results of protein degradation experiments showed that overexpression of Aurora A can reduce the stability of p53.The results of flow cytometry showed that the co-expression of HPV16E6 and Aurora A significantly prevented p53 induced apoptosis.The results of colony formation analysis showed that the co-expression of HPV16E6 and Aurora A significantly reversed the inhibition of colony formation by p53 compared with E6 expression alone.Tumor formation in nude mice showed that tumor volume was smaller in Aurora A silencing nude mice,indicating that the high expression of Aurora A was related to HPV caused tumor formation.Conclusion: Aurora A overexpression reduces p53 stability.Aurora A is involved in E6 inhibition of p53 mediated apoptosis,thus promoting proliferation and inhibiting apoptosis of cervical cancer cells.