HPV16/18 E5, a promising candidate for cervical cancer vaccines, affects SCPs, cell proliferation and cell cycle, and forms a potential network with E6 and E7

Abstract

The spindle checkpoint proteins (SCPs), which sense the existence of misaligned sister chromatids during mitosis and meiosis, are essential for cell proliferation and differentiation. Therefore, the role of SCPs in carcinogenesis is gaining increased attention. In this study, we analysed the expression of Bub1 and Mad2 in clinical samples by immunohistochemistry (IHC) during the development of cervical cancer (CC), and we explored the interaction of Bub1/Mad2 with different proteins through immunoprecipitation (IP). Furthermore, we analysed the characteristics of four different cell models of human papillomavirus (HPV)16/18 E5. We demonstrated that with the progression of CC, the expression of Bub1 and Mad2 was gradually reduced under the influence of HPVE5. Overexpression of HPV16/18 E5 significantly increased cell proliferation, as well as the percentage of cells in the S phase. In addition, the levels of p21, Bub1 and Mad2 were markedly decreased in E5-expressing cells. Therefore, HPV16/18 E5 plays a critical role in carcinogenesis and is a potential therapeutic target in CC treatment.