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Peer-reviewedCC BY-NC 4.0BMB Reports

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

  • Niranjan Kumar1,2
  • Rashmi Rani Sahu1,2
  • Amrita Singh1
  • Akanksha Vyas1,2
  • Saurabh Kumar1
  • Prerona Das1,2
  • Monika Sachdev1,2
  1. 1Division of Endocrinology, CSIR- Central Drug Research Institute, Lucknow 226031, India
  2. 2Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{kumar2026silencing,
  title = {{Silencing of E6/E7 proteins of HPV-16 in the CaCx cell line upregulate the expression of POTE-Paralogs}},
  author = {Niranjan Kumar and Rashmi Rani Sahu and Amrita Singh and Akanksha Vyas and Saurabh Kumar and Prerona Das and Monika Sachdev},
  journal = {BMB Reports},
  year = {2026},
  month = oct,
  doi = {10.5483/bmbrep.2025-0074},
  url = {https://doi.org/10.5483/bmbrep.2025-0074},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Silencing of E6/E7 proteins of HPV-16 in the CaCx cell line upregulate the expression of POTE-Paralogs
AU  - Niranjan Kumar
AU  - Rashmi Rani Sahu
AU  - Amrita Singh
AU  - Akanksha Vyas
AU  - Saurabh Kumar
AU  - Prerona Das
AU  - Monika Sachdev
PY  - 2026
DA  - 2026/10/31
JO  - BMB Reports
DO  - 10.5483/bmbrep.2025-0074
UR  - https://doi.org/10.5483/bmbrep.2025-0074
AB  - 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.
SN  - 1976-6696
SN  - 1976-670X
ER  -