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

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

Author information

1
Department of Medical Genetics, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
2
Department of Pediatric Hematology and Oncology, University Children's Hospital of Cologne, and Center for Molecular Medicine Cologne, University of Cologne, 50924 Cologne, Germany.
3
Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, University of Gothenburg, 405 30 Gothenburg, Sweden.
4
Department of Clinical Genetics, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
5
Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
6
Department of Pediatrics, The Queen Silvia Children's Hospital, 416 85 Gothenburg, Sweden.
7
Department of Women's and Children's Health, Uppsala University, Uppsala University Hospital, 751 85 Uppsala, Sweden.
8
School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
9
BGI-Guangzhou, Guangzhou 510006, China; BGI-Shenzhen, Shenzhen, GuangDong 518083, China.
10
Department of Women's and Children's Health, Uppsala University, Uppsala University Hospital, 751 85 Uppsala, Sweden; Centre for Research and Development, Uppsala University/County Council of Gävleborg, 801 88 Gävle, Sweden.
11
Department of Women's and Children's Health, Karolinska Institutet, 171 76 Stockholm, Sweden.
12
Department of Medical Genetics, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden. Electronic address: kanduri.chandrasekhar@gu.se.

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.

PMID:
25517750
DOI:
10.1016/j.ccell.2014.09.014
[Indexed for MEDLINE]
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