Merkel cell polyomavirus (MCPyV) is a small DNA virus with oncogenic potential. MCPyV is the causative agent of Merkel Cell Carcinoma (MCC), a rare but aggressive tumor of the skin. The role of epigenetic mechanisms, such as histone posttranslational modifications (HPTMs), DNA methylation, and microRNA (miRNA) regulation on MCPyV-driven MCC has recently been highlighted. In this review, we aim to describe and discuss the latest insights into HPTMs, DNA methylation, and miRNA regulation, as well as their regulative factors in the context of MCPyV-driven MCC, to provide an overview of current findings on how MCPyV is involved in the dysregulation of these epigenetic processes. The current state of the art is also described as far as potentially using epigenetic dysregulations and related factors as diagnostic and prognostic tools is concerned, in addition to targets for MCPyV-driven MCC therapy. Growing evidence suggests that the dysregulation of HPTMs, DNA methylation, and miRNA pathways plays a role in MCPyV-driven MCC etiopathogenesis, which, therefore, may potentially be clinically significant for this deadly tumor. A deeper understanding of these mechanisms and related factors may improve diagnosis, prognosis, and therapy for MCPyV-driven MCC.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584046 | PMC |
| http://dx.doi.org/10.3390/ijms222111464 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Merkel cell polyomavirus small tumor antigen contributes to immune evasion by interfering with type I interferon signaling.
PLoS Pathog
August 2024
Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Merkel cell polyomavirus (MCPyV) is the causative agent of the majority of Merkel cell carcinomas (MCC). The virus has limited coding capacity, with its early viral proteins, large T (LT) and small T (sT), being multifunctional and contributing to infection and transformation. A fundamental difference in early viral gene expression between infection and MCPyV-driven tumorigenesis is the expression of a truncated LT (LTtr) in the tumor.
View Article and Find Full Text PDFMerkel cell polyomavirus protein ALTO modulates TBK1 activity to support persistent infection.
PLoS Pathog
July 2024
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
While Merkel cell polyomavirus (MCPyV or MCV) is an abundant virus frequently shed from healthy skin, it is one of the most lethal tumor viruses in immunocompromised individuals, highlighting the crucial role of host immunity in controlling MCPyV oncogenic potential. Despite its prevalence, very little is known about how MCPyV interfaces with the host immune response to maintain asymptomatic persistent infection and how inadequate control of MCPyV infection triggers MCC tumorigenesis. In this study, we discovered that the MCPyV protein, known as the Alternative Large Tumor Open Reading Frame (ALTO), also referred to as middle T, effectively primes and activates the STING signaling pathway.
View Article and Find Full Text PDFDistinct retinoic gene signatures discriminate Merkel cell polyomavirus-positive from -negative Merkel cell carcinoma cells.
J Med Virol
July 2023
Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
Limited molecular knowledge of Merkel cell polyomavirus (MCPyV)-positive and -negative Merkel cell carcinoma (MCC) subsets (MCCP/MCCN) has prevented so far the identification of the MCC origin cell type and, therefore, the development of effective therapies. The retinoic gene signature was investigated in various MCCP, MCCN, and control fibroblast/epithelial cell lines to elucidate the heterogeneous nature of MCC. Hierarchical clustering and principal component analysis indicated that MCCP and MCCN cells were clusterizable from each other and control cells, according to their retinoic gene signature.
View Article and Find Full Text PDFEpigenetic Dysregulations in Merkel Cell Polyomavirus-Driven Merkel Cell Carcinoma.
Int J Mol Sci
October 2021
Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy.
Merkel cell polyomavirus (MCPyV) is a small DNA virus with oncogenic potential. MCPyV is the causative agent of Merkel Cell Carcinoma (MCC), a rare but aggressive tumor of the skin. The role of epigenetic mechanisms, such as histone posttranslational modifications (HPTMs), DNA methylation, and microRNA (miRNA) regulation on MCPyV-driven MCC has recently been highlighted.
View Article and Find Full Text PDFCharacterization of functional domains in the Merkel cell polyoma virus Large T antigen.
Int J Cancer
March 2015
Department of Dermatology, University Hospital, Würzburg, Germany.
Article Synopsis
- Merkel cell carcinoma (MCC) cell growth relies on the MCPyV Large T antigen (LT), specifically the intact retinoblastoma protein (RB)-binding site, unlike other polyomaviruses.
- * Nuclear localization is crucial for LT function, but a specific nuclear localization sequence is not necessary for either LT's nuclear accumulation or MCC cell proliferation.
- * Key regions of the MCPyV, beyond the RB-binding domain, are largely unnecessary for tumor cell growth, but the MUR1 region may stabilize LT expression in MCC cells, while HSC-70 interaction plays a significant role in LT function.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!