title: The risk-associated long noncoding RNA NBAT-1 controls neuroblastoma progression by regulating cell proliferation and neuronal differentiation.
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.
authors.affiliation: Department of Medical Genetics, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Gaurav Kumar
authors.initials: GK
authors.lastname: Pandey
authors.affiliation: Department of Medical Genetics, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Sanhita
authors.initials: S
authors.lastname: Mitra
authors.affiliation: Department of Medical Genetics, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Santhilal
authors.initials: S
authors.lastname: Subhash
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital of Cologne, and Center for Molecular Medicine Cologne, University of Cologne, 50924 Cologne, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Hertwig
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Meena
authors.initials: M
authors.lastname: Kanduri
authors.affiliation: Department of Medical Genetics, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Kankadeb
authors.initials: K
authors.lastname: Mishra
authors.affiliation: Department of Clinical Genetics, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Fransson
authors.affiliation: Department of Medical Genetics, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Abiarchana
authors.initials: A
authors.lastname: Ganeshram
authors.affiliation: Department of Medical Genetics, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Tanmoy
authors.initials: T
authors.lastname: Mondal
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Sashidhar
authors.initials: S
authors.lastname: Bandaru
authors.affiliation: Department of Clinical Genetics, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Ostensson
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Levent M
authors.initials: LM
authors.lastname: Akyürek
authors.affiliation: Department of Pediatrics, The Queen Silvia Children's Hospital, 416 85 Gothenburg, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Abrahamsson
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Uppsala University Hospital, 751 85 Uppsala, Sweden.
authors.forename: Susan
authors.initials: S
authors.lastname: Pfeifer
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Larsson
authors.affiliation: School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Leming
authors.initials: L
authors.lastname: Shi
authors.affiliation: BGI-Guangzhou, Guangzhou 510006, China; BGI-Shenzhen, Shenzhen, GuangDong 518083, China.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital of Cologne, and Center for Molecular Medicine Cologne, University of Cologne, 50924 Cologne, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Fischer
authors.affiliation: Department of Clinical Genetics, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Tommy
authors.initials: T
authors.lastname: Martinsson
authors.affiliation: 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.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Hedborg
authors.affiliation: Department of Women's and Children's Health, Karolinska Institutet, 171 76 Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Kogner
authors.affiliation: Department of Medical Genetics, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden. Electronic address: kanduri.chandrasekhar@gu.se.
authors.forename: Chandrasekhar
authors.initials: C
authors.lastname: Kanduri
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D058953:Neural Stem Cells / Q000502:physiology; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055495:Neurogenesis; D020641:Polymorphism, Single Nucleotide; D062085:RNA, Long Noncoding / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism; D012306:Risk; D059467:Transcriptome; D000099229:RE1-Silencing Transcription Factor
chemical_list: D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor