Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression profiling of human HOS cell line differentiated by beta-glycerophosphate (BGP) treatment

ABSTRACT: Human HOS cell line was differentiated by beta-glycerophosphate (BGP) treatment and gene expression profiling was studied with Illumina expression microarray (HumanHT12_V4). Three negative control replicates vs. three BGP 3-day treatment replicates

ORGANISM(S): Homo sapiens

SUBMITTER: Yuelin Zhu

PROVIDER: E-GEOD-68012 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

miR-23a impairs bone differentiation in osteosarcoma via down-regulation of GJA1.

Gindin Yevgeniy Y Jiang Yuan Y Francis Princy P Walker Robert L RL Abaan Ogan D OD Zhu Yuelin J YJ Meltzer Paul S PS

Frontiers in genetics 20150702

Osteosarcoma is the most common type of bone cancer in children and adolescents. Impaired differentiation of osteoblast cells is a distinguishing feature of this aggressive disease. As improvements in survival outcomes have largely plateaued, better understanding of the bone differentiation program may provide new treatment approaches. The miRNA cluster miR-23a~27a~24-2, particularly miR-23a, has been shown to interact with genes important for bone development. However, global changes in gene ex ...[more]

PMID: 26191074

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Project description:Neuroblastoma tumors frequently show loss of heterozygosity of chromosome 11q with a shortest region of overlap in the 11q23 region. These deletions are thought to cause inactivation of tumor suppressor genes leading to haploinsufficiency. Alternatively, micro-deletions could lead to gene fusion products that are tumor-driving. To identify such events we analyzed a series of neuroblastomas by comparative genomic hybridization (CGH) and single nucleotide polymorphism (SNP) arrays and integrated these data with Affymetrix mRNA profiling data with the bioinformatic tool R2 (http://r2.amc.nl). We identified three neuroblastoma samples with small interstitial deletions at 11q23, upstream of the forkhead-box transcription factor FOXR1. Genes at the proximal side of the deletion were fused to FOXR1, resulting in fusion transcripts of MLL-FOXR1 and PAFAH1B2-FOXR1. FOXR1 expression has only been detected in early embryogenesis. Affymetrix microarray analysis showed high FOXR1 mRNA expression exclusively in the neuroblastomas with micro-deletions and rare cases of other tumor types, including osteosarcoma cell line HOS. RNAi silencing of FOXR1 strongly inhibited proliferation of HOS cells and triggered apoptosis. Expression profiling of these cells and reporter assays suggested that FOXR1 is a negative regulator of forkhead-box factor mediated transcription. The neural crest stem cell line JoMa1 proliferates in culture conditional to activity of a MYC-ER transgene. Over-expression of the wild-type FOXR1 could functionally replace MYC and drive proliferation of JoMa1. We conclude that FOXR1 is recurrently activated in neuroblastoma by intrachromosomal deletion/fusion events, resulting in over-expression of fusion transcripts. Forkhead-box transcription factors have not been previously implicated in neuroblastoma pathogenesis. Furthermore, this is the first identification of intrachromosomal fusion genes in neuroblastoma. Time series Affymetrix U133p2 profiling of Osteosarcoma HOS cells transduced with FOXR1 targeted shRNAs or control shRNA

Dataset Information

Gene expression profiling of human HOS cell line differentiated by beta-glycerophosphate (BGP) treatment

Publications

miR-23a impairs bone differentiation in osteosarcoma via down-regulation of GJA1.

Similar Datasets

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