Epigenetic Dysregulations in Merkel Cell Polyomavirus-Driven Merkel Cell Carcinoma

Int J Mol Sci. 2021 Oct 24;22(21):11464. doi: 10.3390/ijms222111464.

Abstract

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.

Keywords: DNA methylation; HPTMs; Merkel cell carcinoma (MCC); Merkel cell polyomavirus (MCPyV); epigenetics; histone posttranslational modifications; miRNA; microRNA; virus-driven tumors.

Publication types

  • Review

MeSH terms

  • Carcinoma, Merkel Cell* / genetics
  • Carcinoma, Merkel Cell* / pathology
  • Carcinoma, Merkel Cell* / virology
  • DNA Methylation
  • Epigenomics*
  • Histones
  • Humans
  • Merkel cell polyomavirus* / genetics
  • Merkel cell polyomavirus* / pathogenicity
  • MicroRNAs / metabolism
  • Polyomavirus Infections
  • Prognosis
  • Protein Processing, Post-Translational
  • Skin / pathology
  • Skin Neoplasms / pathology
  • Skin Neoplasms / virology

Substances

  • Histones
  • MicroRNAs