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.
- Gaurav Kumar Pandey, Sanhita Mitra, Santhilal Subhash, Falk Hertwig, Meena Kanduri, Kankadeb Mishra, Susanne Fransson, Abiarchana Ganeshram, Tanmoy Mondal, Sashidhar Bandaru, Malin Östensson, Levent M. Akyürek, Jonas Abrahamsson, Susan Pfeifer, Erik Larsson, Leming Shi, Zhiyu Peng, Matthias Fischer, Tommy Martinsson, Fredrik Hedborg, Per Kogner, Chandrasekhar Kanduri. (2014) The Risk-Associated Long Noncoding RNA NBAT-1 Controls Neuroblastoma Progression by Regulating Cell Proliferation and Neuronal Differentiation. Cancer Cell 26(5): 722–737. [abstract]