KAT8 facilitates the proliferation of cancer cells through enhancing E7 function in HPV-associated cervical cancer.

Abstract

Persistent human papillomavirus (HPV) infection serves as the principal etiological factor in cervical cancer, with the oncoprotein E7, which is encoded by the virus, playing a key role in tumorigenesis. However, targeted therapeutic strategies against E7 remain underexplored. KAT8, a lysine acetyltransferase, significantly contributes to oncogenesis through the regulation of transcription. However, its involvement in cervical cancer remains inadequately characterized. This study employs HPV18-positive HeLa and HPV16-positive SiHa cell lines to investigate how KAT8 modulates E7 expression and function in cervical cancer cells. Upon KAT8 knockdown, a marked reduction in cell viability is observed, alongside a decrease in E7 expression. This is associated with elevated level of retinoblastoma protein (pRb) and decreased E2F1 expression, indicating that KAT8 depletion inhibits E7 expression, resulting in E2F1 inactivation and cell cycle arrest. Furthermore, KAT8 directly binds to the promoter regions of the HPV18 LCR, enhancing the transcription of the HPV18 E7 gene. This study also demonstrates that KAT8 is essential for the acetylation of E7 and plays a critical role in facilitating the interaction between pRb/E2F1 and E7 in cervical cancer cells. In conclusion, these results highlight KAT8 as a key driver of cervical cancer progression, promoting the expression of HPV E7 and its associated oncogenic signaling pathways.