The risk-associated long noncoding RNA NBAT-1 controls neuroblastoma progression by regulating cell proliferation and neuronal differentiation

Cancer Cell. 2014 Nov 10;26(5):722-37. doi: 10.1016/j.ccell.2014.09.014. Epub 2014 Nov 10.


Neuroblastoma is an embryonal tumor of the sympathetic nervous system and the most common extracranial tumor of childhood. By sequencing transcriptomes of low- and high-risk neuroblastomas, we detected differentially expressed annotated and nonannotated long noncoding RNAs (lncRNAs). We identified a lncRNA neuroblastoma associated transcript-1 (NBAT-1) as a biomarker significantly predicting clinical outcome of neuroblastoma. CpG methylation and a high-risk neuroblastoma associated SNP on chromosome 6p22 functionally contribute to NBAT-1 differential expression. Loss of NBAT-1 increases cellular proliferation and invasion. It controls these processes via epigenetic silencing of target genes. NBAT-1 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / physiology*
  • Cell Line, Tumor
  • Cell Proliferation*
  • Disease Progression
  • Humans
  • Mice
  • Neoplasm Transplantation
  • Neural Stem Cells / physiology
  • Neuroblastoma / genetics
  • Neuroblastoma / metabolism*
  • Neuroblastoma / pathology
  • Neurogenesis
  • Polymorphism, Single Nucleotide
  • RNA, Long Noncoding / physiology*
  • Repressor Proteins / metabolism
  • Risk
  • Transcriptome


  • Biomarkers, Tumor
  • RE1-silencing transcription factor
  • RNA, Long Noncoding
  • Repressor Proteins