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

Journal article
Authors Gaurav Kumar Pandey
Sanhita Mitra
Santhilal Subhash
Falk Hertwig
Meena Kanduri
Kankadeb Mishra
Susanne Fransson
Abiarchana Ganeshram
Tanmoy Mondal
Sashidar Bandaru
Malin Östensson
Levent Akyürek
Jonas Abrahamsson
Susan Pfeifer
Erik Larsson
Leming Shi
Zhiyu Peng
Matthias Fischer
Tommy Martinsson
Fredrik Hedborg
Per Kogner
Chandrasekhar Kanduri
Published in Cancer Cell
Volume 26
Issue 5
Pages 722-737
ISSN 1535-6108
Publication year 2014
Published at Institute of Biomedicine, Department of Medical and Clinical Genetics
Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 722-737
Language en
Links dx.doi.org/10.1016/j.ccell.2014.09....
Keywords NBAT-1, NBAT1, NBAT, Neuroblastoma, long noncoding RNA, Epigenetics
Subject categories Molecular biology

Abstract

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.

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