Please use this identifier to cite or link to this item: https://doi.org/10.1186/1471-2164-15-S9-S7
Title: HOXD-AS1 is a novel lncRNA encoded in HOXD cluster and a marker of neuroblastoma progression revealed via integrative analysis of noncoding transcriptome
Authors: Yarmishyn, A.A
Batagov, A.O
Tan, J.Z
Sundaram, G.M
Sampath, P 
Kuznetsov, V.A
Kurochkin, I.V
Keywords: long noncoding RNA 1
long noncoding RNA 2
long noncoding RNA 3
long untranslated RNA
phosphatidylinositol 3 kinase
protein kinase B
retinoic acid
transcriptome
tumor marker
unclassified drug
long untranslated RNA
messenger RNA
phosphatidylinositol 3 kinase
protein kinase B
transcription factor
tumor marker
Article
cancer growth
cancer recurrence
cancer staging
cell differentiation
cell nucleus
cohort analysis
controlled study
cytoplasm
gene expression regulation
gene location
gene ontology
gene silencing
genetic association
HOXD AS1 gene
HOXD1 gene
HOXD2 gene
human
human cell
metastasis
microarray analysis
neuroblastoma
primary tumor
signal transduction
tumor gene
upregulation
disease course
gene expression profiling
gene locus
genetics
metabolism
molecular genetics
multigene family
neuroblastoma
pathology
prognosis
tumor cell line
Hominidae
Biomarkers, Tumor
Cell Line, Tumor
Disease Progression
Gene Expression Profiling
Gene Knockdown Techniques
Genetic Loci
Humans
Molecular Sequence Annotation
Multigene Family
Neuroblastoma
Phosphatidylinositol 3-Kinases
Prognosis
Proto-Oncogene Proteins c-akt
RNA, Long Noncoding
RNA, Messenger
Signal Transduction
Transcription Factors
Issue Date: 2014
Citation: Yarmishyn, A.A, Batagov, A.O, Tan, J.Z, Sundaram, G.M, Sampath, P, Kuznetsov, V.A, Kurochkin, I.V (2014). HOXD-AS1 is a novel lncRNA encoded in HOXD cluster and a marker of neuroblastoma progression revealed via integrative analysis of noncoding transcriptome. BMC Genomics 15 : S7. ScholarBank@NUS Repository. https://doi.org/10.1186/1471-2164-15-S9-S7
Rights: Attribution 4.0 International
Abstract: Background: Long noncoding RNAs (lncRNAs) constitute a major, but poorly characterized part of human transcriptome. Recent evidence indicates that many lncRNAs are involved in cancer and can be used as predictive and prognostic biomarkers. Significant fraction of lncRNAs is represented on widely used microarray platforms, however they have usually been ignored in cancer studies. Results: We developed a computational pipeline to annotate lncRNAs on popular Affymetrix U133 microarrays, creating a resource allowing measurement of expression of 1581 lncRNAs. This resource can be utilized to interrogate existing microarray datasets for various lncRNA studies. We found that these lncRNAs fall into three distinct classes according to their statistical distribution by length. Remarkably, these three classes of lncRNAs were co-localized with protein coding genes exhibiting distinct gene ontology groups. This annotation was applied to microarray analysis which identified a 159 lncRNA signature that discriminates between localized and metastatic stages of neuroblastoma. Analysis of an independent patient cohort revealed that this signature differentiates also relapsing from non-relapsing primary tumors. This is the first example of the signature developed via the analysis of expression of lncRNAs solely. One of these lncRNAs, termed HOXD-AS1, is encoded in HOXD cluster. HOXD-AS1 is evolutionary conserved among hominids and has all bona fide features of a gene. Studying retinoid acid (RA) response of SH-SY5Y cell line, a model of human metastatic neuroblastoma, we found that HOXD-AS1 is a subject to morphogenic regulation, is activated by PI3K/Akt pathway and itself is involved in control of RA-induced cell differentiation. Knock-down experiments revealed that HOXD-AS1 controls expression levels of clinically significant protein-coding genes involved in angiogenesis and inflammation, the hallmarks of metastatic cancer. Conclusions: Our findings greatly extend the number of noncoding RNAs functionally implicated in tumor development and patient treatment and highlight their role as potential prognostic biomarkers of neuroblastomas. © 2014 Yarmishyn et al.
Source Title: BMC Genomics
URI: https://scholarbank.nus.edu.sg/handle/10635/181475
ISSN: 14712164
DOI: 10.1186/1471-2164-15-S9-S7
Rights: Attribution 4.0 International
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