RNF8 induces β-catenin-mediated c-Myc expression and promotes colon cancer proliferation

Int J Biol Sci. 2020 May 1;16(12):2051-2062. doi: 10.7150/ijbs.44119. eCollection 2020.

Abstract

DNA damage signals transducer RING finger protein 8 (RNF8) is involved in maintaining genomic stability by facilitating the repair of DNA double-strand breaks (DSB) via ubiquitin signaling. By analyzing the TCGA database and colon cancer tissue microarrays, we found that the expression level of RNF8 was positively correlated with that of c-Myc in colon cancer, which were closely associated with poor survival of colon cancer patients. Furthermore, overexpressing and knocking down RNF8 increased and decreased the expression of c-Myc in colon cancer cells, respectively. In addition, RNF8 interacted with β-catenin and facilitated its nuclear translocation by conjugating K63 polyubiquitination on it. These observations suggested a de novo role of RNF8 in promoting the progression of colon cancer by inducing β-catenin-mediated c-Myc expression.

Keywords: RNF8; c-Myc; colon cancer; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • DNA-Binding Proteins
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • RNF8 protein, human
  • beta Catenin
  • Ubiquitin-Protein Ligases