The Risk-Associated Long Noncoding RNA NBAT-1Controls Neuroblastoma Progression by RegulatingCell Proliferation and Neuronal Differentiation
2014 (English)In: Cancer Cell, ISSN 1535-6108, E-ISSN 1878-3686, Vol. 26, no 5, 722-737 p.Article in journal (Refereed) Published
Neuroblastoma is an embryonal tumor of the sympathetic nervous system and the most common extracranial tumor of childhood. By sequencing transcriptonnes 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.
Place, publisher, year, edition, pages
2014. Vol. 26, no 5, 722-737 p.
Cancer and Oncology
IdentifiersURN: urn:nbn:se:uu:diva-238013DOI: 10.1016/j.ccell.2014.09.014ISI: 000344980900015PubMedID: 25517750OAI: oai:DiVA.org:uu-238013DiVA: diva2:769825