Project description:The aims of this study are to compare transcripts that are differentially expressed in the MYCN amplified compare to the MYCN non-amplified neuroblastoma cell lines, in particular, long non-coding RNAs. Methods: Ribosomal depleted RNAs from six human neuroblastoma cell lines were subjected to deep sequencing, using Illumina Hiseq. Results: We identified 459 transcripts are differentially expressed betweeen the MYCN amplified and the MYCN non-amplified cell lines. Conclusions: We have identified a novel long noncoding RNA lncNB1 that is highly expressed in the MYCN amplified compared to the MYCN non-amplified cell lines.
Project description:The MYCN locus is amplified in about half of high-risk neuroblastoma tumors. To identify genomic loci occupied by MYCN protein in the MYCN-amplified neuroblastoma cell lines NGP, Kelly and NB-1643, we performed chromatin immunoprecipitation coupled with Next-Generation Sequencing (ChIP-seq) using an anti-MYCN antibody.
Project description:Understanding the aberrant transcriptional landscape of neuroblastoma is necessary to provide insight to the underlying influences of the initiation, progression and persistence of this developmental cancer. Here, we present chromatin immunoprecipitation sequencing (ChIP-Seq) data for the oncogenic transcription factors, MYCN and MYC, as well as regulatory histone marks H3K4me1, H3K4me3, H3K27Ac, and H3K27me3 in ten commonly used human neuroblastoma-derived cell line models. In addition, for all of the profiled cell lines we provide ATAC-Seq as a measure of open chromatin. We validate specificity of global MYCN occupancy in MYCN amplified cell lines and functional redundancy of MYC occupancy in MYCN non-amplified cell lines. Finally, we show with H3K27Ac ChIP-Seq that these cell lines retain expression of key neuroblastoma super-enhancers (SE). We anticipate this dataset, coupled with available transcriptomic profiling on the same cell lines, will enable the discovery of novel gene regulatory mechanisms in neuroblastoma. This SuperSeries is composed of the SubSeries listed below.
Project description:Neuroblastoma is the third most common pediatric cancer and is responsible for approximately 15% of all childhood cancer deaths (Maris & Matthay, 1999). In our analysis, we found that poor patient survival with increasing mRNA expression level of AURKA and AURKB in Mycn-amplified neuroblastoma. In the light of this evidence, we were able to find possibilities of existing inhibitors for therapy. According to the following experiments, we found that tozasertib, a pan-Aurora kinase inhibitor, has high therapeutic potential in neuroblastoma treatment. First, we performed in vitro experiments to reveal that tozasertib suppressed cell proliferation in multiple Mycn-amplified neuroblastoma cell lines. Next, we evaluated ex vivo not only in Mycn-amplified neuroblastoma xenograft mouse model but also TH-Mycn transgenic mouse model. The results showed that tozasertib significantly inhibited the tumor growth and prolonged the survival probability in both animal models. Finally, we explored the mechanism of tozasertib-treated tissues in two animal models by iTRAQ proteomic.
