The novel long noncoding RNA lncUSMycN in N-Myc-induced oncogenesis
type: CreativeWork
description: One of the worst subtypes of neuroblastoma is caused by the amplification of a 130 kb genomic DNA region containing the MYCN oncogene. While MYCN has been extensively investigated, it is unknown whether other genomic elements within the 130 kb amplicon play a role in neuroblastoma. In this study, I experimentally validated the novel long noncoding RNA up-stream of MYCN (lncUSMycN), which was originally annotated by bioinformatics analyses, within the 130 kb amplicon. Using rapid amplification of cDNA ends PCR, 140 extra nucleotides at the 5’-end of lncUSMycN were identified. Gene copy number analysis of human neuroblastoma samples showed that the lncUSMycN gene was co-amplified with MYCN, leading to lncUSMycN RNA over-expression. Repression of lncUSMycN decreased N-Myc mRNA expression and cell proliferation in MYCN amplified neuroblastoma cells. Microarray differential gene expression studies demonstrated that lncUSMycN regulated the expression of N-Myc target genes at genome-wide level. RNA-binding protein pull-down assays identified NonO as a lncUSMycN RNA binding protein, and RNA-immunoprecipitation assays showed that NonO bound to lncUSMycN and N-Myc RNAs. While knocking down NonO and lncUSMycN expression reduced N-Myc mRNA expression, forced over-expression of lncUSMycN resulted in N-Myc mRNA up-regulation by binding to NonO. ChIP assays showed that neither lncUSMycN nor NonO bound to the MYCN gene promoter to alter histone H3 trimethylation at lysine 4, a marker for active gene transcription, indicating that lncUSMycN up-regulated N-Myc mRNA expression through a post-transcriptional mechanism. Pearson correlation and Kaplan-Meier survival analyses demonstrated that high levels of lncUSMycN and NonO RNA expression in human neuroblastoma tissues correlated with high levels of N-Myc mRNA expression and predicted poor prognoses in three independent cohorts of neuroblastoma patients. Multivariable Cox regression analyses showed that high levels of lncUSMycN and Non…
abstract: One of the worst subtypes of neuroblastoma is caused by the amplification of a 130 kb genomic DNA region containing the MYCN oncogene. While MYCN has been extensively investigated, it is unknown whether other genomic elements within the 130 kb amplicon play a role in neuroblastoma. In this study, I experimentally validated the novel long noncoding RNA up-stream of MYCN (lncUSMycN), which was originally annotated by bioinformatics analyses, within the 130 kb amplicon. Using rapid amplification of cDNA ends PCR, 140 extra nucleotides at the 5’-end of lncUSMycN were identified. Gene copy number analysis of human neuroblastoma samples showed that the lncUSMycN gene was co-amplified with MYCN, leading to lncUSMycN RNA over-expression. Repression of lncUSMycN decreased N-Myc mRNA expression and cell proliferation in MYCN amplified neuroblastoma cells. Microarray differential gene expression studies demonstrated that lncUSMycN regulated the expression of N-Myc target genes at genome-wide level. RNA-binding protein pull-down assays identified NonO as a lncUSMycN RNA binding protein, and RNA-immunoprecipitation assays showed that NonO bound to lncUSMycN and N-Myc RNAs. While knocking down NonO and lncUSMycN expression reduced N-Myc mRNA expression, forced over-expression of lncUSMycN resulted in N-Myc mRNA up-regulation by binding to NonO. ChIP assays showed that neither lncUSMycN nor NonO bound to the MYCN gene promoter to alter histone H3 trimethylation at lysine 4, a marker for active gene transcription, indicating that lncUSMycN up-regulated N-Myc mRNA expression through a post-transcriptional mechanism. Pearson correlation and Kaplan-Meier survival analyses demonstrated that high levels of lncUSMycN and NonO RNA expression in human neuroblastoma tissues correlated with high levels of N-Myc mRNA expression and predicted poor prognoses in three independent cohorts of neuroblastoma patients. Multivariable Cox regression analyses showed that high levels of lncUSMycN and Non…
author: Liu, Pei Yan
language: EN
keywords: N-Myc, lncRNA, lncUSMycN
license: https://purl.org/coar/access_right/c_abf2
license: https://creativecommons.org/licenses/by-nc-nd/3.0/au/
date published: 2014
date modified: 2026-07-24T05:32:53Z
provider: University of New South Wales
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: UNSW, Sydney

PropertyValue
property ID: Handle
value: http://hdl.handle.net/1959.4/54469

PropertyValue
property ID: DOI
value: 10.26190/unsworks/2757