The oncogenic roles of JC polyomavirus T antigen in cervical cancer

Abstract

BackgroundAccording to pathological and transgenic data, there is a close link between JC polyomavirus (JCPyV) T antigen and various epithelial cancers. The aim of this study was to explore the role of T antigen in cervical tumorigenesis.MethodsThe phenotypes were observed in T antigen-overexpressing HeLa cells by Cell Counting Kit-8 assay, Annexin V staining, Transwell assay, and a xenograft model. Phenotype-related and T antigen partner proteins were screened by western blot. Nested, real-time, and in situ PCR were used to detect T antigen in cervical cancer.ResultsOverexpression of T antigen promoted the proliferation, anti-apoptosis, anti-pyroptosis, chemoresistance, migration, invasion, and epithelial-mesenchymal transition of HeLa cells. All mutants impaired the positively regulated effects of T antigen on proliferation. According to a general PCR, the positive rate of T antigen was higher in cervical cancer than in adjacent cervical intraepithelial neoplasia (CIN) and normal tissues (p < 0.05), in line with the JCPyV copy number (p < 0.05). T antigen-positive cells were detectable in the nuclei of cervical cancer, CIN, and squamous cells by in situ PCR. Strong nuclear immunoreactivity against T antigen was observed in cervical cancers, but not in CIN or normal squamous epithelium.ConclusionsJCPyV T antigen may insert into the genome of cervical squamous epithelial cells and encode T antigen for its oncogenesis. T antigen participates in the aggressive progression of these cells by promoting proliferation, anti-apoptosis, anti-pyroptosis, migration, invasion, epithelial-mesenchymal transition, and chemoresistance.