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SRP011378
Homo sapiens
3 Downloadable Samples
Illumina Genome Analyzer II
Description
In adult cancers, epigenetic changes and aberrant splicing of the DNMT3B is commonly observed, and the pattern of gene methylation and expression has been shown to be modified by DNMT3B7, a truncated protein of DNMT3B. Much less is known about the mechanism of epigenetic changes in the pediatric cancer neuroblastoma. To investigate if aberrant DNMT3B transcripts alter DNA methylation, gene expression and tumor phenotype in neuroblastoma, we measured DNMT3B isoform expression in primary tumors and cell lines. Higher levels of DNMT3B7 were detected in differentiated ganglioneuroblastomas compared to undifferentiated neuroblastomas, suggesting that expression of DNMT3B7 may induce a less clinically aggressive tumor phenotype. To test this hypothesis, we investigated the effects of forced DNMT3B7 in neuroblastoma cells. We found that DNMT3B7 expression significantly inhibited neuroblastoma cell proliferation in vitro, and in neuroblastoma xenografts, DNMT3B7 decreased angiogenesis and tumor growth. DNMT3B7-positive cells had higher levels of total genomic methylation, and RNA-sequencing revealed a dramatic decrease in expression of FOS and JUN family members, AP1 complex components. Consistent with the established antagonistic relationship between AP1 expression and retinoic acid receptor activity, decreased proliferation and increased differentiation was seen in the DNMT3B7-expressing neuroblastoma cells following treatment with all trans retinoic acid (ATRA) compared to controls. Our results demonstrate that high levels of DNMT3B7 modify the epigenome in neuroblastoma cells, induce changes in gene expression, inhibit tumor growth, and increase sensitivity to ATRA. Further knowledge regarding mechanisms by which DNMT3B7 regulates gene methylation may ultimately lead to the development of therapeutic strategies that reverse the epigenetic aberrations that drive neuroblastoma pathogenesis. Overall design: DNMT3B7, a truncated DNMT3B isoform, was stably transfected into an N-type neuroblastoma cell line (LA1-55n) using a Tet-off inducible system. DNMT3B7 expressing cells were compared to vector control cells after 21 days of induction.
Publication Title
Truncated DNMT3B isoform DNMT3B7 suppresses growth, induces differentiation, and alters DNA methylation in human neuroblastoma.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 159 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
We investigated the molecular mechanisms of chronic alcohol consumption or lipopolysaccharide insult by gene expression profiling in prefrontal cortex and liver of C57BL/6J mice.
Publication Title
Gene expression in brain and liver produced by three different regimens of alcohol consumption in mice: comparison with immune activation.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Production of functional proteins requires multiple steps including gene transcription and post-translational processing. MicroRNAs (miRNA) can regulate individual stages of these processes. Despite the importance of the cystic fibrosis transmembrane conductance regulator (CFTR) channel for epithelial anion transport, how its expression is regulated remains uncertain. We discovered that microRNA-138 regulates CFTR expression through its interactions with the transcriptional regulatory protein SIN3A. Treating airway epithelia with a miR-138 mimic increased CFTR mRNA and also enhanced CFTR abundance and transepithelial Cl- permeability independently of elevated mRNA levels. A miR-138 anti-miR had the opposite effects. Importantly, miR-138 altered the expression of many genes encoding proteins that associate with CFTR and may influence its biosynthesis. The most common CFTR mutation, F508, causes protein misfolding, degradation, and cystic fibrosis. Remarkably, manipulating the miR-138 regulatory network also improved biosynthesis of CFTR-F508 and restored Cl- transport to cystic fibrosis airway epithelia. This novel miRNA-regulated network directs gene expression from the chromosome to the cell membrane, indicating that an individual miRNA can control a cellular process broader than previously recognized. This discovery also provides new therapeutic avenues for restoring CFTR function to cells affected by the most common cystic fibrosis mutation.
Publication Title
A microRNA network regulates expression and biosynthesis of wild-type and DeltaF508 mutant cystic fibrosis transmembrane conductance regulator.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Sus scrofa
- 121 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A high protein diet during pregnancy affects hepatic gene expression of energy sensing pathways along ontogenesis in a porcine model.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 67 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptional response of skeletal muscle to a low-protein gestation diet in porcine offspring accumulates in growth- and cell cycle-regulating pathways.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 62 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
German landrace gilts were fed a high protein diet (HP, 30% CP) throughout their whole pregnancy. Subsequently hepatic transcriptome profiles of the offspring were analysed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn)
Publication Title
A high protein diet during pregnancy affects hepatic gene expression of energy sensing pathways along ontogenesis in a porcine model.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 59 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
German landrace gilts were fed an adequate protein diet (AP, 12% CP) throughout their whole pregnancy. Subsequently hepatic transcriptome profiles of the offspring were analysed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn).
Publication Title
A high protein diet during pregnancy affects hepatic gene expression of energy sensing pathways along ontogenesis in a porcine model.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 24 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
German landrace gilts were fed a high protein diet (HP, 30% CP) throughout their whole pregnancy. Subsequently muscle transcriptome profiles of the offspring were analysed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn)
Publication Title
Transcriptional response of skeletal muscle to a low-protein gestation diet in porcine offspring accumulates in growth- and cell cycle-regulating pathways.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 23 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
German landrace gilts were fed a low protein diet (LP, 6% CP) throughout their whole pregnancy. Subsequently muscle transcriptome profiles of the offspring were analysed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn)
Publication Title
Transcriptional response of skeletal muscle to a low-protein gestation diet in porcine offspring accumulates in growth- and cell cycle-regulating pathways.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 20 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
German landrace gilts were fed an adequate protein diet (AP, 12% CP) throughout their whole pregnancy. Subsequently muscle transcriptome profiles of the offspring were analysed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn)
Publication Title
Transcriptional response of skeletal muscle to a low-protein gestation diet in porcine offspring accumulates in growth- and cell cycle-regulating pathways.
Sample Metadata Fields
Specimen part
View Samples