• Microbiology and Biotechnology Letters
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• v.51 no.2
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• pp.135-146
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• 2023

Viral oncology is focused on understanding the relationship between cancer and viruses, which are known to play a role in the development of certain types of cancer. Approximately 15-20% of human cancers are believed to be caused by oncogenic viruses, and as a result, there is significant interest in understanding how these viruses contribute to cancer development. There are several viruses that have been linked to cancer, including human papillomavirus, hepatitis B and C virus, Epstein-Barr virus, human T-cell lymphotropic virus type 1, Kaposi's sarcoma-associated herpesvirus, and Merkel cell polyomavirus. Each of these viruses is associated with different types of cancer, and the mechanisms by which they contribute to cancer development are diverse. This article discusses these mechanisms as well as current and future strategies for preventing and treating virus-associated cancers with the goal of presenting a thorough review of the current state of knowledge in viral oncology and to highlight the importance of continued research in this field.

• Molecules and Cells
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• v.44 no.3
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• pp.146-159
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• 2021

DNA methylation, and consequent down-regulation, of tumour suppressor genes occurs in response to epigenetic stimuli during cancer development. Similarly, human oncoviruses, including human papillomavirus (HPV), up-regulate and augment DNA methyltransferase (DNMT) and histone deacetylase (HDAC) activities, thereby decreasing tumour suppressor genes (TSGs) expression. Ubiquitin-like containing PHD and RING finger domain 1 (UHRF1), an epigenetic regulator of DNA methylation, is overexpressed in HPV-induced cervical cancers. Here, we investigated the role of UHRF1 in cervical cancer by knocking down its expression in HeLa cells using lentiviral-encoded short hairpin (sh)RNA and performing cDNA microarrays. We detected significantly elevated expression of thioredoxin-interacting protein (TXNIP), a known TSG, in UHRF1-knockdown cells, and this gene is hypermethylated in cervical cancer tissue and cell lines, as indicated by whole-genome methylation analysis. Up-regulation of UHRF1 and decreased TXNIP were further detected in cervical cancer by western blot and immunohistochemistry and confirmed by Oncomine database analysis. Using chromatin immunoprecipitation, we identified the inverted CCAAT domain-containing UHRF1-binding site in the TXNIP promoter and demonstrated UHRF1 knockdown decreases UHRF1 promoter binding and enhances TXNIP expression through demethylation of this region. TXNIP promoter CpG methylation was further confirmed in cervical cancer tissue by pyrosequencing and methylation-specific polymerase chain reaction. Critically, down-regulation of UHRF1 by siRNA or UHRF1 antagonist (thymoquinone) induces cell cycle arrest and apoptosis, and ubiquitin-specific protease 7 (USP7), which stabilises and promotes UHRF1 function, is increased by HPV viral protein E6/E7 overexpression. These results indicate HPV might induce carcinogenesis through UHRF1-mediated TXNIP promoter methylation, thus suggesting a possible link between CpG methylation and cervical cancer.