A LIN28B-RAN-AURKA Signaling Network Promotes Neuroblastoma Tumorigenesis

Robert W. Schnepp, Priya Khurana, Edward F. Attiyeh, Pichai Raman, Sara E. Chodosh, Derek A. Oldridge, Maria E. Gagliardi, Karina L. Conkrite, Shahab Asgharzadeh, Robert C. Seeger, Blair B. Madison, Anil K. Rustgi, John M. Maris, Sharon J. Diskin

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)599-609
Number of pages11
JournalCancer Cell
Volume28
Issue number5
DOIs
StatePublished - Nov 9 2015

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