Identification of DEIN, a Novel Gene with High Expression Levels in Stage IVS Neuroblastoma

Abstract

Neuroblastoma at stage IVS, defined by dissemination to specific tissues and age <1 year at diagnosis, regularly follows spontaneous regression without cytotoxic treatment. To uncover the molecular characteristics of this subtype, Serial Analysis of Gene Expression (SAGE) profiles from stage IVS and fatal stage IV tumors were compared. A SAGE tag (GCAACTTAAC) was detected that was overrepresented in stage IVS disease and that had no reliable match in current National Center for Biotechnology Information databases of SAGE profiles, thus pointing to a novel gene. The corresponding gene, which maps to chromosome 4q33-34, was identified using a modified 3 ¶-and 5 ¶-rapid amplification of cDNA ends PCR and was designated as DEIN (differentially expressed in neuroblastoma). The gene comprises five transcript variants and its sequence overlaps with expressed sequences of the yet uncharacterized UniGene cluster Hs.61435. DEIN exhibits nucleotide sequence conservation over a broad range of species with an overall homology of 65% between human and mouse. As none of the predicted amino acid sequences is homologous to known proteins, it remains to be determined whether DEIN represents a coding or noncoding RNA. Northern blot analysis and semiquantitative reverse transcription-PCR showed high DEIN expression in neuroblastoma, whereas expression was absent or weak in most normal adult tissues. Analysis of 121 primary neuroblastomas by real-time reverse transcription-PCR revealed a strong association with age at diagnosis <1 year and particularly with stage IVS disease (both P < 0.001). The characteristic expression pattern of DEIN suggests a specific role of this gene in the unique biology of stage IVS tumors and may help to molecularly define this special subtype of neuroblastoma. (Mol Cancer Res 2007;5(12):1276 -84)

N-myc and Noncoding RNAs in Neuroblastoma

“…DEIN has been shown to be differentially expressed in neuroblastoma subtypes, with higher expression in tumors with good prognosis and spontaneous regression (children <1 year and in Stage IVS). No significant association between DEIN and MYCN amplification was reported (94). The expression of DEIN has been shown to be tightly linked to expression of the PHOX2B-downstream target HAND2 through a bidirectional promoter.…”

Competing endogenous RNA network analysis identifies critical genes among the different breast cancer subtypes

“…Therefore, the dysfunction of the enriched tumor suppressor genes probably drives the initiation and progression of breast cancer. Several cancer associated lncRNAs including the common ceRNA hubs like HAND2-AS1 (DEIN) [44, 45] and RP11-276H19.1 [46], as well as subtype-specific hubs like ADAMTS9-AS2, a luminal A specific hub lncRNA, acted as tumor suppressors and inhibited the migration of the glioma cells [47]. Similarly, functional analysis of the miRNA hubs by the TAM tool showed that the common and specific miRNA hubs play important roles in breast cancer subtypes (Supplementary Table 8) [48].…”

Identification of important long non-coding RNAs and highly recurrent aberrant alternative splicing events in hepatocellular carcinoma through integrative analysis of multiple RNA-Seq datasets

“…Significant methylation was found in the promoter region of LAMC3 in breast cancer (Kuznetsova et al 2007). HAND2-AS1, also known as DEIN, was first identified by Voth et al (2007) displaying high expression level in stage IVS neuroblastoma. Similarly, Lin and Chuang (2012) found repressed expression of LINC00261 in primary cultured invasive phenotype HCC cells compared Fig.…”