Abstract 3668: A LIN28B-PBK Axis promotes neuroblastoma dissemination and aggression

LIN28B is an RNA binding protein that plays key roles in normal development and, when deregulated, oncogenesis; mechanistically, it blocks the processing of the let-7 family of tumor suppressors and binds mRNAs directly. We previously demonstrated that LIN28B induces neuroblastoma proliferation, in part by regulating the expression of RAN GTPase and Aurora kinase A (AURKA). However, given the widespread metastases seen within neuroblastoma, we speculated that LIN28B might also influence neuroblastoma dissemination. We used gain and loss of function approaches to genetically manipulate transcripts of interest in neuroblastoma cells and measured effects on self-renewal, invasion, and downstream signaling. To examine the impact of LIN28B on dissemination, we generated GFP-luciferase expressing neuroblastoma cell line models in which LIN28B levels were manipulated, injected these lines into the tail veins of NSG mice, and tracked dissemination using an IVIS Spectrum system. Results show that depletion of LIN28B significantly delayed the onset of tumor metastasis, reduced tumor burden, and extended mouse survival (104 days versus 50 days, p