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.
Lipid degradation promotes prostate cancer cell survival.
No sample metadata fields
View SamplesThe dataset consists of 266 NCCN very low/low or favorable-intermediate risk PCa patients who underwent diagnostic prostate biopsy between 2000 and 2014 and were treated with RP in six community or academic practices: University of Calgary, Cedars-Sinai, Spectrum Health, Cleveland Clinic, MD Anderson Cancer Center and Johns Hopkins. All patients had complete tumor pathology from biopsy and prostatectomy. Low risk PCa was defined as T1c or cT2a, and Gleason score (GS) 6, and PSA < 10ng/ml and favorable-intermediate risk was no greater than predominant GS 3 and percent positive biopsy cores < 50%, and either cT2b-cT2c or PSA 10-20ng/ml.
Validation of the Decipher Test for predicting adverse pathology in candidates for prostate cancer active surveillance.
Age, Specimen part
View Samplesneuroblastoma cells derived from PDOX models were treated with the kinase inhibitor. Overall design: 5 repetitions of control and IBL-302 treated cells were harvest and submitted for RNAseq analysis
Anti-tumor effects of PIM/PI3K/mTOR triple kinase inhibitor IBL-302 in neuroblastoma.
Specimen part, Treatment, Subject
View SamplesThe Hippo pathway is an emerging signaling cascade involved in the regulation of organ size control. It consists of evolutionally conserved protein kinases that are sequentially phosphorylated and activated. The active Hippo pathway subsequently phosphorylates a transcription coactivator, YAP, which precludes its nuclear localization and transcriptional activation. Identification of transcriptional targets of YAP in diverse cellular contexts is therefore critical to the understanding of the molecular mechanisms in which the Hippo pathway restricts tissue growth.
Hippo signaling regulates microprocessor and links cell-density-dependent miRNA biogenesis to cancer.
Specimen part
View SamplesWe analyzed samples from 770 male human subjects who are part of the METSIM study. Ethics Committee of the Northern Savo Hospital District approved the study. All participants gave written informed consent. The population-based cross-sectional METSIM study included 10 197 men, aged from 45 to 73 years, who were randomly selected from the population register of the Kuopio town in eastern Finland (population 95000). Every participant had a 1-day outpatient visit to the Clinical Research Unit at the University of Kuopio, including an interview on the history of previous diseases and current drug treatment and an evaluation of glucose tolerance and cardiovascular risk factors. After 12 h of fasting, a 2 h oral 75 g glucose tolerance test was performed and the blood samples were drawn at 0, 30 and 120 min. Plasma glucose was measured by enzymatic hexokinase photometric assay (Konelab Systems reagents; Thermo Fischer Scientific, Vantaa, Finland). Insulin was determined by immunoassay (ADVIA Centaur Insulin IRI no. 02230141; Siemens Medical Solutions Diagnostics, Tarrytown, NY, USA). Height and weight were measured to the nearest 0.5 cm and 0.1 kg, respectively. Waist circumference (at the midpoint between the lateral iliac crest and lowest rib) and hip circumference (at the level of the trochanter major) were measured to the nearest 0.5 cm. Body composition was determined by bioelectrical impedance (RJL Systems) in subjects in the supine position.
Genetic Regulation of Adipose Gene Expression and Cardio-Metabolic Traits.
Sex, Age, Specimen part
View SamplesHere we harnessed the potential of RNA sequencing in 89 human pancreatic islet donors to identify genes and exons regulated in this relevant tissue for T2D. Overall design: mRNA profiles of 89 human pancreatic islet donors having different levels of blood glucose (HbA1c) with and without T2D. The data was generated by deep sequencing using Illumina HiSeq 2000.
Orphan G-protein coupled receptor 183 (GPR183) potentiates insulin secretion and prevents glucotoxicity-induced β-cell dysfunction.
Sex, Age, Specimen part, Subject
View SamplesThese patients proved resistant to docetaxel treatment, exhibiting residual tumor of 25% or greater remaining volume.
Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer.
No sample metadata fields
View SamplesThese patients were sensitive to docetaxel treatment, exhibiting less than 25% residual tumor.
Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Patterns of resistance and incomplete response to docetaxel by gene expression profiling in breast cancer patients.
No sample metadata fields
View SamplesSingle-cell RNA-seq (10X Genomics Chromium) to profile of cardiac progenitor cells, comparing the transcriptomes of diploid and tetraploid cardiac progenitor cells Overall design: Transcriptional profiling of diploid and tetraploid CPCs by scRNA-Seq approaches using 10X Genomics Chromium
Cardiac interstitial tetraploid cells can escape replicative senescence in rodents but not large mammals.
Sex, Specimen part, Cell line, Subject
View Samples