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Viruses and Cancers
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Viruses and Cancers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 10832

Special Issue Editor

Prof. Dr. Rui Medeiros

E-Mail Website
Guest Editor
Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal
Interests: molecular oncology; cancer cachexia; precision medicine; pharmacogenomics; prognostic biomarkers; predictive biomarkers; microRNAs; genetic polymorphism; viral nucleic acids
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is estimated that at least 10 % of worldwide cancers may be attributable to viral infection with a strong impact on survival and quality of life. Oncogenic viruses include various classes of DNA and RNA viruses. The viruses associated with the greatest number of cancer cases are the human papillomaviruses (HPVs), which cause cervical cancer and several other epithelial malignancies, and Hepatitis B virus (HBV) and hepatitis C virus (HCV), which are responsible for the majority of hepatocellular cancer. Other oncoviruses include Epstein–Barr virus (EBV), human T-cell leukemia virus (HTLV-I), Kaposi's sarcoma-associated herpes virus (KSHV), and Merkel cell polyomavirus (MCV).

In this Special Issue, we welcome submissions of research and review articles on the molecular mechanisms that contribute to virus-induced carcinogenesis, including papers on the role of oncoviral proteins in cell transformation, the gene mutational profile of viral and host genomes, expression levels of miRNAs, gene methylation, immune responses, and new therapeutic opportunities (including cancer vaccines for viruses-related cancers). Furthermore, we welcome submissions on the impact of COVID-19/SARS-CoV-2 and oncogenic virus associated diseases.

Prof. Dr. Rui Medeiros
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (3 papers)

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Research

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19 pages, 2777 KiB  
Article
Regulation of Transcriptional Activity of Merkel Cell Polyomavirus Large T-Antigen by PKA-Mediated Phosphorylation
by Mar Falquet, Carla Prezioso, Maria Ludvigsen, Jack-Ansgar Bruun, Sara Passerini, Baldur Sveinbjørnsson, Valeria Pietropaolo and Ugo Moens
Int. J. Mol. Sci. 2023, 24(1), 895; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24010895 - 03 Jan 2023
Cited by 1 | Viewed by 4498
Abstract
Merkel cell polyomavirus (MCPyV) is the major cause of Merkel cell carcinoma (MCC), an aggressive skin cancer. MCPyV large T-antigen (LTag) and small T-antigen (sTag) are the main oncoproteins involved in MCPyV-induced MCC. A hallmark of MCPyV-positive MCC cells is the expression of [...] Read more.
Merkel cell polyomavirus (MCPyV) is the major cause of Merkel cell carcinoma (MCC), an aggressive skin cancer. MCPyV large T-antigen (LTag) and small T-antigen (sTag) are the main oncoproteins involved in MCPyV-induced MCC. A hallmark of MCPyV-positive MCC cells is the expression of a C-terminal truncated LTag. Protein kinase A (PKA) plays a fundamental role in a variety of biological processes, including transcription by phosphorylating and thereby regulating the activity of transcription factors. As MCPyV LTag has been shown to be phosphorylated and acts as a transcription factor for the viral early and late promoter, we investigated whether LTag can be phosphorylayted by PKA, and whether this affects the transcript activity of LTag. Using a phosphorylation prediction algorithm, serine 191, 203, and 265 were identified as putative phosphorylation sites for PKA. Mass spectrometry of in vitro PKA-phosphorylated peptides confirmed phosphorylation of S203 and S265, but not S191. Full-length LTag inhibited early and late promoter activity of MCPyV, whereas the truncated MKL2 LTag variant stimulated both promoters. Single non-phosphorylable, as well as phosphomimicking mutations did not alter the inhibitory effect of full-length LTag. However, the non-phosphorylable mutations abrogated transactivation of the MCPyV promoters by MKL2 LTag, whereas phosphomimicking substitutions restored the ability of MKL2 LTag to activate the promoters. Triple LTag and MKL2 LTag mutants had the same effect as the single mutants. Activation of the PKA signaling pathway did not enhance MCPyV promoter activity, nor did it affect LTag expression levels in MCPyV-positive Merkel cell carcinoma (MCC) cells. Our results show that phosphorylation of truncated LTag stimulates viral promoter activity, which may contribute to higher levels of the viral oncoproteins LTag and sTag. Interfering with PKA-induced LTag phosphorylation/activity may be a therapeutic strategy to treat MCPyV-positive MCC patients. Full article
(This article belongs to the Special Issue Viruses and Cancers)
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14 pages, 839 KiB  
Article
P16 and HPV Genotype Significance in HPV-Associated Cervical Cancer—A Large Cohort of Two Tertiary Referral Centers
by Sara da Mata, Joana Ferreira, Inmaculada Nicolás, Susana Esteves, Gonçalo Esteves, Sofia Lérias, Fernanda Silva, Adela Saco, Daniela Cochicho, Mário Cunha, Marta del Pino, Jaume Ordi and Ana Félix
Int. J. Mol. Sci. 2021, 22(5), 2294; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052294 - 25 Feb 2021
Cited by 12 | Viewed by 2557
Abstract
The expression of p16 is a good surrogate of human papillomavirus (HPV) infection in HPV-associated cancers. The significance of p16 expression, HPV genotype and genera in the outcome of patients with HPV-associated cervical cancer (CC) is unclear. Our aim is to ascertain the [...] Read more.
The expression of p16 is a good surrogate of human papillomavirus (HPV) infection in HPV-associated cancers. The significance of p16 expression, HPV genotype and genera in the outcome of patients with HPV-associated cervical cancer (CC) is unclear. Our aim is to ascertain the prognostic significance of these factors. Data from 348 patients (median age: 47.5 years old) with CC, diagnosed in two referral centers, were retrospectively collected. Advanced disease (FIGO2018 IB2-IV) was present in 68% of patients. A single HPV genotype was identified in 82.8% of patients. The most common HPVs were HPV16 (69%) and HPV18 (14%). HPV genera reflected this distribution. HPV16 tumors presented at an earlier stage. P16 was negative in 18 cases (5.2%), 83.3% of which were squamous cell carcinomas. These cases occurred in older patients who tended to have advanced disease. In the univariate analysis, HPV16 (HR: 0.58; p = 0.0198), α-9 genera (HR: 0.37; p = 0.0106) and p16 overexpression (HR: 0.54; p = 0.032) were associated with better survival. HPV16 (HR: 0.63; p = 0.0174) and α-9 genera (HR: 0.57; p = 0.0286) were associated with less relapse. In the multivariate analysis, only the International Federation of Gynecology and Obstetrics (FIGO) stage retained an independent prognostic value. HPV16, α-9 genera and p16 overexpression were associated with better survival, although not as independent prognostic factors. Patients with p16-negative HPV-associated CC were older, presented with advanced disease and had worse prognosis. Full article
(This article belongs to the Special Issue Viruses and Cancers)
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Review

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31 pages, 2571 KiB  
Review
Viruses in Cancers of the Digestive System: Active Contributors or Idle Bystanders?
by Martin Marônek, René Link, Giovanni Monteleone, Roman Gardlík and Carmine Stolfi
Int. J. Mol. Sci. 2020, 21(21), 8133; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218133 - 30 Oct 2020
Cited by 13 | Viewed by 3052
Abstract
The human virome, which is a collection of all the viruses that are present in the human body, is increasingly being recognized as an essential part of the human microbiota. The human gastrointestinal tract and related organs (e.g., liver, pancreas, and gallbladder)—composing the [...] Read more.
The human virome, which is a collection of all the viruses that are present in the human body, is increasingly being recognized as an essential part of the human microbiota. The human gastrointestinal tract and related organs (e.g., liver, pancreas, and gallbladder)—composing the gastrointestinal (or digestive) system—contain a huge number of viral particles which contribute to maintaining tissue homeostasis and keeping our body healthy. However, perturbations of the virome steady-state may, both directly and indirectly, ignite/sustain oncogenic mechanisms contributing to the initiation of a dysplastic process and/or cancer progression. In this review, we summarize and discuss the available evidence on the association and role of viruses in the development of cancers of the digestive system. Full article
(This article belongs to the Special Issue Viruses and Cancers)
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