Open AccessRDM 1 promotes neuroblastoma growth through the RAS –Raf– MEK – ERK pathway
Author(s) -
Xie Guojin,
Wu Haiyan,
Cai Weiluo,
Chen Mo,
Huang Wending,
Yan Wangjun,
Chang Yong
Publication year - 2019
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12586
Subject(s) - mapk/erk pathway , protein kinase a , cell growth , microbiology and biotechnology , kinase , cell cycle , chemistry , apoptosis , cancer research , biology , biochemistry
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 .