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accession-icon SRP066238
Lipid degradation promotes prostate cancer cell survival
  • organism-icon Homo sapiens
  • sample-icon 12 Downloadable Samples
  • Technology Badge IconIlluminaHiSeq2000

Description

Prostate cancer is the most common male cancer and androgen receptor (AR) is the major driver of the disease. Here we show that Enoyl-CoA delta isomerase 2 (ECI2) is a novel AR-target that promotes prostate cancer cell survival. Increased ECI2 expression predicts mortality in prostate cancer patients (p=0.0086). ECI2 encodes for an enzyme involved in lipid metabolism, and we use multiple metabolite profiling platforms and RNA-seq to show that inhibition of ECI2 expression leads to decreased glucose utilization, accumulation of fatty acids and down-regulation of cell cycle related genes. In normal cells, decrease in fatty acid degradation is compensated by increased consumption of glucose, and here we demonstrate that prostate cancer cells are not able to respond to decreased fatty acid degradation. Instead, prostate cancer cells activate incomplete autophagy, which is followed by activation of the cell death response. Finally, we identified a clinically approved compound, perhexiline, which inhibits fatty acid degradation, and replicates the major findings for ECI2 knockdown. This work shows that prostate cancer cells require lipid degradation for survival and identifies a small molecule inhibitor with therapeutic potential. Overall design: Two biological replicates for prostate cancer cell line (LNCaP) and cell line representing normal prostate epithelium (RWPE-1), transfected with scrambled siRNA or two different siRNAs targeting ECI2. RNA was extracted and used for RNA-sequencing. The processed files provided are compressed folders containing multiple output files from CuffDiff runs estimating differentially expressed transcripts between the indicated ECI2 siRNA treated cells versus cells treated with Scrambled siRNAs.

Publication Title

Lipid degradation promotes prostate cancer cell survival.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE41171
The histone demethylase Jarid1b ensures faithful mouse development by protecting developmental genes from aberrant H3K4me3 [Affymetrix]
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Embryonic development is tightly regulated by transcription factors and chromatin-associated proteins. H3K4me3 is associated with active transcription and H3K27me3 with gene repression, while the combination of both keeps genes required for development in a plastic state. Here we show that deletion of the H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) results in major neonatal lethality due to respiratory failure. Jarid1b knockout embryos have several neural defects including disorganized cranial nerves, defects in eye development and increased incidences of exencephaly. Moreover, in line with an overlap of Jarid1b and Polycomb targets genes, Jarid1b knockout embryos display homeotic skeletal transformations typical for Polycomb mutants. Genome-wide analysis demonstrated that normally inactive genes encoding developmental regulators acquire aberrant H3K4me3 in early Jarid1b knockout embryos. H3K4me3 accumulates as embryonic development proceeds, leading to increased expression of neural master regulators in knockouts. Taken together, these results suggest that Jarid1b contributes to mouse development by protecting developmental genes from inappropriate acquisition of active histone modifications.

Publication Title

The histone demethylase Jarid1b ensures faithful mouse development by protecting developmental genes from aberrant H3K4me3.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE10919
Transgenerational epigenetic programming of the embryonic testis transcriptome
  • organism-icon Rattus norvegicus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Genome 230 2.0 Array (rat2302)

Description

Embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination appears to promote an epigenetic reprogramming of the male germ line that is associated with transgenerational adult-onset disease states. Transgenerational effects on the embryonic day 16 (E16) testis demonstrated reproducible changes in the testis transcriptome for multiple generations (F1-F3). The expression of 196 genes was found to be influenced, with the majority of gene expression being decreased or silenced. Dramatic changes in the gene expression of methyltransferases during gonadal sex determination were observed in the F1 and F2 vinclozolin generation (E16) embryonic testis, but the majority returned to control-generation levels by the F3 generation. The most dramatic effects were on the germ-line-associated Dnmt3A and Dnmt3L isoforms. Observations demonstrate that an embryonic exposure to vinclozolin appears to promote an epigenetic reprogramming of the male germ line that correlates with transgenerational alterations in the testis transcriptome in subsequent generations.

Publication Title

Transgenerational epigenetic programming of the embryonic testis transcriptome.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE39824
Expression data from Chicken duodenum
  • organism-icon Gallus gallus
  • sample-icon 16 Downloadable Samples
  • Technology Badge Icon Affymetrix Chicken Genome Array (chicken)

Description

The objective of this study was to decipher the molecular basis of feed efficiency in meat-type chicken using duodenum tissues from a chicken population divergently selected for residual feed intake (RFI). Residual feed intake is the deviation of expected feed intake from actual feed intake. Chickens that consume less feed than expected are efficient (LRFI) and chickens that consume more feed than expected are inefficient (HRFI). A divergent selection for RFI was undertaken using an unselected random bred chicken population. RFI at day 35-42 was used as a criterion for selecting low (LRFI) and high (HRFI) RFI. Duodenum tissues were collected from 16 male chickens under sterile conditions experimentation. Tissues were collected from 4 males at days 35 and 42 in each line.

Publication Title

Transcriptomic analysis to elucidate the molecular mechanisms that underlie feed efficiency in meat-type chickens.

Sample Metadata Fields

Specimen part

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accession-icon SRP040772
miRNome of endometriotic lesion
  • organism-icon Homo sapiens
  • sample-icon 11 Downloadable Samples
  • Technology Badge IconIlluminaGenomeAnalyzer

Description

miRNA high-throughput sequencing was used to investigate endometriosis lesion-specific miRNA expression profiles by comparing a set of paired samples of peritoneal endometriotic lesions and matched healthy surrounding tissue together with eutopic endometrium of the same patients. We found that miRNAs of surrounding peritoneal tissue mask most of the miRNA expression differences that could originate from endometriotic tissue and thus only miRNAs with significantly different levels in the endometriotic lesions compared to peritoneal tissue were detected. According to the results of this study, two miRNAs – miR-34c and miR-449a showed remarkably higher expression in lesions compared to healthy tissue. Overall design: Eleven tissue samples (two endometria, five peritoneal lesions and four matched adjacent normal-appearing tissues) were analysed from two patients with a histologically confirmed diagnosis of moderate-severe endometriosis (III-IV stage)

Publication Title

High-throughput sequencing approach uncovers the miRNome of peritoneal endometriotic lesions and adjacent healthy tissues.

Sample Metadata Fields

No sample metadata fields

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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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