Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

RNA-sequencing of human pancreatic adenocarcinoma cancer tissues

ABSTRACT: RNA-seq profiling was conducted on clinically-annotated human pancreatic adenocarcinoma cancer tissues We measured the transcriptome in 51 clinically-annotated human pancreatic adenocarcinoma cancer tissues

ORGANISM(S): Homo sapiens

SUBMITTER: Marie Kirby

PROVIDER: E-GEOD-79668 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

RNA sequencing of pancreatic adenocarcinoma tumors yields novel expression patterns associated with long-term survival and reveals a role for ANGPTL4.

Kirby Marie K MK Ramaker Ryne C RC Gertz Jason J Davis Nicholas S NS Johnston Bobbi E BE Oliver Patsy G PG Sexton Katherine C KC Greeno Edward W EW Christein John D JD Heslin Martin J MJ Posey James A JA Grizzle William E WE Vickers Selwyn M SM Buchsbaum Donald J DJ Cooper Sara J SJ Myers Richard M RM

Molecular oncology 20160526 8

<h4>Background</h4>Pancreatic adenocarcinoma patients have low survival rates due to late-stage diagnosis and high rates of cancer recurrence even after surgical resection. It is important to understand the molecular characteristics associated with survival differences in pancreatic adenocarcinoma tumors that may inform patient care.<h4>Results</h4>RNA sequencing was performed for 51 patient tumor tissues extracted from patients undergoing surgical resection, and expression was associated with o ...[more]

PMID: 27282075

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Project description:The liver x receptor (LXR) and peroxisome proliferator-activated receptor gamma (PPARG) nuclear receptor transcription factors (TFs) are master regulators of energy homeostasis that impact tumor cell metabolism and proliferation. To better define the underlying molecular processes governing the genetic control of cellular growth in response to extracellular metabolic signals, we performed a comprehensive, genome-wide characterization of the temporal regulatory cascades mediated by LXR and PPARG signaling in HT29 colorectal cancer cells. For this analysis we applied a multi-tiered approach that incorporated cellular phenotypic assays, gene expression profiles, chromatin state dynamics and nuclear receptor binding patterns. By integrating these orthogonal datasets over time, we uncovered the regulatory architecture of LXR and PPARG activity. Both sets of nuclear receptors inhibited cell proliferation and increased cellular oxidative stress, validating results from independent studies. Despite this metabolic reprogramming, the gene regulatory network programs initiated by these nuclear receptors were widely distinct. PPARG generated a rapid and short-term response while maintaining a gene activator role. By contrast, LXR signaling was prolonged, with initial, predominantly activating functions altering to repressive gene regulatory activities at late time points through RNA polymerase II (RNAP2) promoter pausing. This exhaustive dataset illustrates the complexity of genome function and structure by elucidating how common phenotypic outcomes are genetically encoded through diverse transcriptional programs. Our results further provide a detailed, molecular framework that can be applied to better understanding how extracellular nutrients impact cancer cell physiology and highlight the importance of study designs that incorporate complementary genomic features in a dynamic manner. ChIP-seq and RNA-seq experiments were performed in HT29 cells using vehicle control (DMSO) or after drug treatment (GW3965 and rosiglitazone).

Dataset Information

RNA-sequencing of human pancreatic adenocarcinoma cancer tissues

Publications

RNA sequencing of pancreatic adenocarcinoma tumors yields novel expression patterns associated with long-term survival and reveals a role for ANGPTL4.

Similar Datasets

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