NCYM promotes calpain-mediated Myc-nick production in human MYCN-amplified neuroblastoma cells

Biochem Biophys Res Commun. 2015 Jun 5;461(3):501-6. doi: 10.1016/j.bbrc.2015.04.050. Epub 2015 Apr 17.

Abstract

NCYM is a cis-antisense gene of MYCN and is amplified in human neuroblastomas. High NCYM expression is associated with poor prognoses, and the NCYM protein stabilizes MYCN to promote proliferation of neuroblastoma cells. However, the molecular mechanisms of NCYM in the regulation of cell survival have remained poorly characterized. Here we show that NCYM promotes cleavage of MYCN to produce the anti-apoptotic protein, Myc-nick, both in vitro and in vivo. NCYM and Myc-nick were induced at G2/M phase, and NCYM knockdown induced apoptotic cell death accompanied by Myc-nick downregulation. These results reveal a novel function of NCYM as a regulator of Myc-nick production in human neuroblastomas.

Keywords: Calpain; Cell cycle; MYCN; Myc-nick; NCYM; Neuroblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Division
  • Cell Line, Tumor
  • G2 Phase
  • Genes, myc
  • Humans
  • In Situ Nick-End Labeling
  • N-Myc Proto-Oncogene Protein
  • Neuroblastoma / genetics
  • Neuroblastoma / metabolism*
  • Neuroblastoma / pathology
  • Nuclear Proteins / genetics*
  • Oncogene Proteins / genetics*
  • Real-Time Polymerase Chain Reaction

Substances

  • MYCN protein, human
  • N-Myc Proto-Oncogene Protein
  • Nuclear Proteins
  • Oncogene Proteins