Gene Expression Profile Analysis of Human Epidermal Keratinocytes Expressing Human Papillomavirus Type 8 E7

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Abstract

Background: Human papillomavirus type 8 (HPV8) has been implicated in the progress of non-melanoma skin cancers and their precursor lesions. The HPV8 E7 oncoprotein plays a key role in the tumorigenesis of HPV-associated cutaneous tumors. However, the exact role of HPV8 E7 in human epidermal carcinogenesis has not been fully elucidated.

Methods: To investigate the potential carcinogenic effects of HPV8 E7 on epithelial cells, we used RNA-sequencing technology to analyze the gene expression profile of HPV8 E7-overexpressed normal human epidermal keratinocytes (NHEKs).

Results: RNA-sequencing revealed 831 differentially expressed genes (DEGs) between HPV8 E7-expressing NHEKs and control cells, among which, 631 genes were significantly upregulated, and 200 were downregulated. Gene ontology annotation enrichment analysis showed that HPV8 E7 mainly affected the expression of genes associated with protein heterodimerization activity, DNA binding, nucleosomes, and nucleosome assembly. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that overexpression of HPV8 E7 affected the expression of gene clusters associated with viral carcinogenesis and transcriptional misregulation in cancer and necroptosis signaling pathways that reportedly play crucial roles in HPV infection promotion and cancer progression. We also found the DEGs, such as HKDC1 and TNFAIP3, were associated with epigenetic modifications, immune regulation, and metabolic pathways.

Conclusion: Our results demonstrate that the pro-carcinogenic effect of HPV8 expression in epithelial cells may be attributed to the regulatory effect of oncogene E7 on gene expression associated with epigenetic modifications and immune and metabolic status-associated gene expression. Although our data are based on an in vitro experiment, it provides the theoretical evidence that the development of squamous cell carcinoma can be caused by HPV.

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KEGG: integrating viruses and cellular organisms

Minoru Kanehisa, Miho Furumichi, Yoko Sato … (2020)

Abstract KEGG (https://www.kegg.jp/) is a manually curated resource integrating eighteen databases categorized into systems, genomic, chemical and health information. It also provides KEGG mapping tools, which enable understanding of cellular and organism-level functions from genome sequences and other molecular datasets. KEGG mapping is a predictive method of reconstructing molecular network systems from molecular building blocks based on the concept of functional orthologs. Since the introduction of the KEGG NETWORK database, various diseases have been associated with network variants, which are perturbed molecular networks caused by human gene variants, viruses, other pathogens and environmental factors. The network variation maps are created as aligned sets of related networks showing, for example, how different viruses inhibit or activate specific cellular signaling pathways. The KEGG pathway maps are now integrated with network variation maps in the NETWORK database, as well as with conserved functional units of KEGG modules and reaction modules in the MODULE database. The KO database for functional orthologs continues to be improved and virus KOs are being expanded for better understanding of virus-cell interactions and for enabling prediction of viral perturbations.

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The Gene Ontology Resource: 20 years and still GOing strong

Jurg Bahler (2019)

Abstract The Gene Ontology resource (GO; http://geneontology.org) provides structured, computable knowledge regarding the functions of genes and gene products. Founded in 1998, GO has become widely adopted in the life sciences, and its contents are under continual improvement, both in quantity and in quality. Here, we report the major developments of the GO resource during the past two years. Each monthly release of the GO resource is now packaged and given a unique identifier (DOI), enabling GO-based analyses on a specific release to be reproduced in the future. The molecular function ontology has been refactored to better represent the overall activities of gene products, with a focus on transcription regulator activities. Quality assurance efforts have been ramped up to address potentially out-of-date or inaccurate annotations. New evidence codes for high-throughput experiments now enable users to filter out annotations obtained from these sources. GO-CAM, a new framework for representing gene function that is more expressive than standard GO annotations, has been released, and users can now explore the growing repository of these models. We also provide the ‘GO ribbon’ widget for visualizing GO annotations to a gene; the widget can be easily embedded in any web page.

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Carcinogenic human papillomavirus infection.

Bradley Monk, Carole Fakhry, Silvia Sanjosé … (2016)

Infections with human papillomavirus (HPV) are common and transmitted by direct contact. Although the great majority of infections resolve within 2 years, 13 phylogenetically related, sexually transmitted HPV genotypes, notably HPV16, cause - if not controlled immunologically or by screening - virtually all cervical cancers worldwide, a large fraction of other anogenital cancers and an increasing proportion of oropharyngeal cancers. The carcinogenicity of these HPV types results primarily from the activity of the oncoproteins E6 and E7, which impair growth regulatory pathways. Persistent high-risk HPVs can transition from a productive (virion-producing) to an abortive or transforming infection, after which cancer can result after typically slow accumulation of host genetic mutations. However, which precancerous lesions progress and which do not is unclear; the majority of screening-detected precancers are treated, leading to overtreatment. The discovery of HPV as a carcinogen led to the development of effective preventive vaccines and sensitive HPV DNA and RNA tests. Together, vaccination programmes (the ultimate long-term preventive strategy) and screening using HPV tests could dramatically alter the landscape of HPV-related cancers. HPV testing will probably replace cytology-based cervical screening owing to greater reassurance when the test is negative. However, the effective implementation of HPV vaccination and screening globally remains a challenge.

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Author and article information

Contributors

Hao Cheng: URI : https://loop.frontiersin.org/people/1359723/overview

Journal

Journal ID (nlm-ta): Pathol Oncol Res

Journal ID (iso-abbrev): Pathol Oncol Res

Journal ID (publisher-id): Pathol. Oncol. Res.

Title: Pathology and Oncology Research

Publisher: Frontiers Media S.A.

ISSN (Print): 1219-4956

ISSN (Electronic): 1532-2807

Publication date (Electronic): 18 May 2022

Publication date Collection: 2022

Volume: 28

Electronic Location Identifier: 1610176

Affiliations

[1] ¹ Department of Dermatology and Venereology , Zhejiang University School of Medicine Sir Run Run Shaw Hospital , Hangzhou, China

[2] ² Department of Dermatology , Zhejiang Provincial People’s Hospital , People’s Hospital of Hangzhou Medical College , Hangzhou, China

[3] ³ Department of Gastroenterology , Zhejiang University School of Medicine Sir Run Run Shaw Hospital , Hangzhou, China

Author notes

Edited by: Krenács Tibor, Semmelweis University, Hungary

*Correspondence: Yinjing Song, 3315023@ 123456zju.edu.cn ; Hao Cheng, chenghao1@ 123456zju.edu.cn

[ † ]

These authors have contributed equally to this work

Article

Publisher ID: 1610176

DOI: 10.3389/pore.2022.1610176

PMC ID: 9156622

SO-VID: 780448f5-3d75-4249-97e4-a31abe0826c4

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 04 November 2021

Date accepted : 21 April 2022

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Gene Expression Profile Analysis of Human Epidermal Keratinocytes Expressing Human Papillomavirus Type 8 E7

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Most cited references 45

KEGG: integrating viruses and cellular organisms

The Gene Ontology Resource: 20 years and still GOing strong

Carcinogenic human papillomavirus infection.

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