A LIN28B-RAN-AURKA Signaling Network Promotes Neuroblastoma Tumorigenesis
Menée sur des lignées cellulaires et à partir d'échantillons de tissu tumoral et de sang prélevés sur 250 patients pédiatriques atteints d'un neuroblastome, cette étude met en évidence des mécanismes par lesquels la signalisation LIN28B-RAN-AURKA favorise le développement de la maladie
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.