<scp>RDM</scp>1 promotes neuroblastoma growth through the <scp>RAS</scp>–Raf–<scp>MEK</scp>–<scp>ERK</scp> pathway

Abstract

Neuroblastoma ( NB ) is an aggressive cancer that originates in the sympathetic nervous system and primarily affects children. Here, we show that high levels of RAD 52 motif containing 1 ( RDM 1; a protein with similarities to RAD 52, which is important for double‐strand DNA repair) are associated with poor clinical outcomes for NB . In addition, RDM 1 −/− cells exhibited increased sensitivity to cisplatin, a common chemotherapy drug, and disruption of RDM 1 suppressed NB cell proliferation. We also report that loss of RDM 1 augmented cell apoptosis and induced cell cycle arrest, and that stable knockdown of RDM 1 significantly inhibited NB tumor growth in a xenograft mouse model. Importantly, we identified that RDM 1 promoted cell proliferation via the RAS –Raf–mitogen‐activated protein kinase kinase ( MEK )–extracellular signal‐regulated kinase ( ERK ) signaling pathway. In conclusion, the current study demonstrates a correlation between DNA damage regulator RDM 1 and the oncogenic RAS –Raf– MEK – ERK pathway in NB .