A LIN28B-RAN-AURKA Signaling Network Promotes Neuroblastoma Tumorigenesis.
A LIN28B-RAN-AURKA Signaling Network Promotes Neuroblastoma Tumorigenesis.
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DOI：
10.1016/j.ccell.2015.09.012
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发表时间：
2015-11-09
期刊：
影响因子：
50.3
通讯作者：
Diskin SJ
中科院分区：
文献类型：
--
作者：
Schnepp RW;Khurana P;Attiyeh EF;Raman P;Chodosh SE;Oldridge DA;Gagliardi ME;Conkrite KL;Asgharzadeh S;Seeger RC;Madison BB;Rustgi AK;Maris JM;Diskin SJ
A more complete understanding of aberrant oncogenic signaling in neuroblastoma, a malignancy of the developing sympathetic nervous system, is paramount to improving patient outcomes. Recently, we identified LIN28B as an oncogenic driver in high-risk neuroblastoma. Here, we identify the oncogene RAN as a LIN28B target and show regional gain of chromosome 12q24 as an additional somatic alteration resulting in increased RAN expression. We show that LIN28B influences RAN expression by promoting RAN Binding Protein 2 expression and by directly binding RAN mRNA. Further, we demonstrate a convergence of LIN28B and RAN signaling on Aurora kinase A activity. Collectively, these findings demonstrate that LIN28B-RAN-AURKA signaling drives neuroblastoma oncogenesis, suggesting that this pathway may be amenable to therapeutic targeting.
