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

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. •NCYM promotes cleavages of MYC and MYCN to produce Myc-nick in vitro.•NCYM increases Myc-nick production in MYCN-amplified neuroblastoma cells.•NCYM knockdown decreases Myc-nick production and induces apoptosis at G2/M phase.