Silencing of E6/E7 proteins of HPV-16 in the CaCx cell line upregulate the expression of POTE-Paralogs.

POTE proteins are known to be expressed in tissues such as normal prostate, placenta, ovary, testis, and embryo, and are collectively referred to as POTE-family proteins based on this organ-specific expression. The POTE gene spans 32 kb on chromosome 21q11.2, although its homologous genes are distributed across eight different chromosomes. POTEE, as a member of the POTE family, has been identified as a Cancer Germline Antigen (CGA) across several cancer types including Colorectal, Pancreatic, Breast, Liver, and Lung cancers. This study aims to elucidate the role of POTE-Paralogs (POTEE & POTEF) as CGA markers in Cervical Cancer (CaCx). Over 90% of CaCx cases are associated with persistent infection by high-risk HPV (HR-HPV); the E6 and E7 oncoproteins of HPV contribute to carcinogenesis through the degradation or inactivation of tumor suppressor proteins p53 and pRB, leading to uncontrolled cell proliferation. Consequently, HPV-positive cervical cancer cell lines HeLa and CaSki lack detectable expression of p53, and the expression of POTE-Paralogs is also markedly decreased, while the HPV-negative CaCx cell line C-33A exhibits high p53 expression correlated with marked upregulation of POTE-Paralogs. Treatment of C-33A cells with a p53-specific inhibitor reduced POTE-Paralogs expression. Conversely, restoring p53 expression in CaSki cells with the chemotherapeutic agent Doxorubicin resulted in increased expression of POTE-Paralogs. Furthermore, silencing of E6/E7 in CaSki cells led to restoration of both p53 and pRB expression, as well as an increase in POTEE & POTEF levels.