HOXD-AS1 is a novel lncRNA encoded in HOXD cluster and a marker of neuroblastoma progression revealed via integrative analysis of noncoding transcriptome.

摘要: 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 prognostic biomarkers. Significant fraction is represented on widely microarray platforms, however they have usually been ignored studies. We developed computational pipeline to annotate popular Affymetrix U133 microarrays, creating resource allowing measurement expression 1581 lncRNAs. This utilized interrogate existing datasets for various lncRNA found these fall into three distinct classes according their statistical distribution by length. Remarkably, were co-localized with protein coding genes exhibiting gene ontology groups. annotation was applied analysis which identified 159 signature discriminates between localized metastatic stages neuroblastoma. Analysis an independent patient cohort revealed this differentiates also relapsing from non-relapsing primary tumors. the first example via solely. One lncRNAs, termed HOXD-AS1, encoded HOXD cluster. HOXD-AS1 evolutionary conserved among hominids has all bona fide features gene. Studying retinoid acid (RA) response SH-SY5Y cell line, model neuroblastoma, we subject morphogenic regulation, activated PI3K/Akt pathway itself control RA-induced differentiation. Knock-down experiments controls levels clinically significant protein-coding angiogenesis inflammation, hallmarks cancer. Our findings greatly extend number functionally implicated tumor development treatment highlight role potential biomarkers neuroblastomas.