The DNMT1/PCNA/UHRF1 disruption induces tumorigenesis characterized by similar genetic and epigenetic signatures

Sci Rep. 2014 Mar 18:4:4230. doi: 10.1038/srep04230.

Abstract

Several genetic and epigenetic signatures characterize cancer cells. However, the relationships (causal or consequence link, existence due to a same origin) between these 2 types of signatures were not fully elucidated. In the present work, we reported that the disruption of the DNMT1/PCNA/UHRF1 complex acts as an oncogenic event of the tumor transformation of brain (astrocytes), breast, lung and mesothelial cells. We also show that these tumor transformation processes were associated with the acquisition of cancer hallmark and common genetic and epigenetic signatures. Thus, our data revealed that the global DNA hypomethylation induced by the DNMT1/PCNA/UHRF1 disruption is an oncogenic event of human tumorigenesis, an inducer of epigenetic and genetic signatures frequently observed in several human cancers, and is an initiator of oncogenic events.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Brain / metabolism
  • Brain / pathology
  • CCAAT-Enhancer-Binding Proteins / genetics*
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • Cell Line
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methylation
  • Epigenesis, Genetic*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Epithelium / metabolism
  • Epithelium / pathology
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung / metabolism
  • Lung / pathology
  • Mammary Glands, Human / metabolism
  • Mammary Glands, Human / pathology
  • Proliferating Cell Nuclear Antigen / genetics*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • Ubiquitin-Protein Ligases

Substances

  • CCAAT-Enhancer-Binding Proteins
  • Proliferating Cell Nuclear Antigen
  • Recombinant Fusion Proteins
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNMT1 protein, human
  • UHRF1 protein, human
  • Ubiquitin-Protein Ligases