HPV16 E1 dysregulated cellular genes involved in cell proliferation and host DNA damage: A possible role in cervical carcinogenesis

Baedyananda, Fern, Chaiwongkot, Arkom, Varadarajan, Shankar ORCID: 0000-0002-8827-6567 and Bhattarakosol, Parvapan (2021) HPV16 E1 dysregulated cellular genes involved in cell proliferation and host DNA damage: A possible role in cervical carcinogenesis. PLOS ONE, 16 (12). e0260841-.

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Official URL: http://dx.doi.org/10.1371/journal.pone.0260841

Abstract

HPV16 is the most prominent cause of cervical cancer. HPV16 E1, a helicase required for HPV replication exhibits increased expression in association with cervical cancer progression, suggesting that E1 has a similar effect on the host as the HPV16 E6 and E7 oncoproteins. This study aimed to determine whether expression of HPV16 E1 correlated with carcinogenesis by modulating cellular pathways involved in cervical cancer. HEK293T cells were transfected with pEGFP, pEGFPE1 or truncated forms of HPV16 E1. Cell proliferation, cell death, and the impact of HPV16 E1 on host gene expression was then evaluated. HPV16 E1 overexpression resulted in a significant reduction of cell viability and cellular proliferation (p-value<0.0001). Moreover, prolonged expression of HPV16 E1 significantly induced both apoptotic and necrotic cell death, which was partially inhibited by QVD-OPH, a broad-spectrum caspase inhibitor. Microarray, real time RT-PCR and kinetic host gene expression analyses revealed that HPV16 E1 overexpression resulted in the downregulation of genes involved in protein synthesis (RPL36A), metabolism (ALDOC), cellular proliferation (CREB5, HIF1A, JMJDIC, FOXO3, NFKB1, PIK3CA, TSC22D3), DNA damage (ATR, BRCA1 and CHEK1) and immune response (ISG20) pathways. How these genetic changes contribute to HPV16 E1-mediated cervical carcinogenesis warrants further studies.

Item Type:	Article
Uncontrolled Keywords:	Cell Line, Tumor, Humans, DNA Damage, Necrosis, Oncogene Proteins, Viral, Signal Transduction, Apoptosis, Cell Proliferation, Gene Expression Regulation, Neoplastic, Uterine Cervical Neoplasms, Female, Host-Pathogen Interactions, HEK293 Cells, Carcinogenesis, Protein Domains
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	23 May 2022 09:32
Last Modified:	18 Jan 2023 21:01
DOI:	10.1371/journal.pone.0260841
Open Access URL:	https://doi.org/10.1371/journal.pone.0260841
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3155338