The Risk-Associated Long Noncoding RNA NBAT-1 Controls Neuroblastoma Progression by Regulating Cell Proliferation and Neuronal Differentiation.. Neuroblastoma transcriptome sequencing.

Neuroblastoma is one of the most common extracranial solid tumors in children. By sequencing transcriptomes of low- and high-risk neuroblastomas, we have identified differentially expressed annotated and novel long noncoding RNAs (lncRNAs). Our analysis identifies a lncRNA neuroblastoma associated transcript-1 (NBAT-1) as a biomarker for predicting the clinical outcome of the neuroblastoma patients. CpG methylation and a high-risk neuroblastoma associated SNP on chromosome 6p22 functionally contribute to differential expression of NBAT-1. Loss of NBAT-1 results in increased proliferation and invasion of cells. It controls these processes via epigenetic silencing of target genes. Its loss affects neuronal differentiation through activation of the neuronal-specific transcription factor NRSF/REST. Thus, loss of NBAT-1 contributes to aggressive neuroblastoma by increasing proliferation and impairing differentiation of neuronal precursors.