Similar Datasets
Project description:The biological properties of pancreatic cancer stem cells (PCSCs) remain incompletely defined and the central regulators are unknown. By bioinformatic analysis of a PCSC-enriched gene signature, we identified the transcription factor HNF1A as a putative central regulator of PCSC function. Levels of HNF1A and its target genes were found to be elevated in PCSCs and tumorspheres, and depletion of HNF1A resulted in growth inhibition, apoptosis, impaired tumorsphere formation, PCSC depletion, and downregulation of OCT4 expression. Conversely, HNF1A overexpression increased PCSC numbers and tumorsphere formation in pancreatic cancer cells and drove PDA cell growth. Importantly, depletion of HNF1A in primary tumor xenografts impaired tumor growth and depleted PCSCs in vivo. Finally, we established an HNF1A-dependent gene signature in PDA cells that significantly correlated with reduced survivability in patients. These findings identify HNF1A as a central transcriptional regulator of the PCSC state and novel oncogene in pancreatic ductal adenocarcinoma.
2018-09-04 | GSE108149 | GEO
Project description:The biological properties of pancreatic cancer stem cells (PCSCs) remain incompletely defined and the central regulators are unknown. By bioinformatic analysis of a PCSC-enriched gene signature, we identified the transcription factor HNF1A as a putative central regulator of PCSC function. Levels of HNF1A and its target genes were found to be elevated in PCSCs and tumorspheres, and depletion of HNF1A resulted in growth inhibition, apoptosis, impaired tumorsphere formation, PCSC depletion, and downregulation of OCT4 expression. Conversely, HNF1A overexpression increased PCSC numbers and tumorsphere formation in pancreatic cancer cells and drove PDA cell growth. Importantly, depletion of HNF1A in primary tumor xenografts impaired tumor growth and depleted PCSCs in vivo. Finally, we established an HNF1A-dependent gene signature in PDA cells that significantly correlated with reduced survivability in patients. These findings identify HNF1A as a central transcriptional regulator of the PCSC state and novel oncogene in pancreatic ductal adenocarcinoma.
2018-09-04 | GSE108150 | GEO
Project description:The biological properties of pancreatic cancer stem cells (PCSCs) remain incompletely defined and the central regulators are unknown. By bioinformatic analysis of a human PCSC-enriched gene signature, we identified the transcription factor HNF1A as a putative central regulator of PCSC function. Levels of HNF1A and its target genes were found to be elevated in PCSCs and tumorspheres, and depletion of HNF1A resulted in growth inhibition, apoptosis, impaired tumorsphere formation, decreased PCSC marker expression, and downregulation of POU5F1/OCT4 expression. Conversely, HNF1A overexpression increased PCSC marker expression and tumorsphere formation in pancreatic cancer cells and drove pancreatic ductal adenocarcinoma (PDA) cell growth. Importantly, depletion of HNF1A in xenografts impaired tumor growth and depleted PCSC marker-positive cells in vivo. Finally, we established an HNF1A-dependent gene signature in PDA cells that significantly correlated with reduced survivability in patients. These findings identify HNF1A as a central transcriptional regulator of PCSC properties and novel oncogene in PDA.
| S-EPMC6122955 | biostudies-literature
Project description:HNF1A is a Novel Oncogene and Central Regulator of Pancreatic Cancer Stem Cells
| PRJNA422591 | ENA
Project description:HNF1A is a Novel Oncogene and Central Regulator of Pancreatic Cancer Stem Cells [Bru-seq]
| PRJNA422593 | ENA
Project description:HNF1A is a Novel Oncogene and Central Regulator of Pancreatic Cancer Stem Cells [ChIP-seq]
| PRJNA422594 | ENA
Project description:In genome-wide association (GWA) studies, hundreds of thousands of single-nucleotide polymorphisms (SNP) are tested for association with a disease trait. Typically, GWA studies give equal consideration to all SNPs tested, regardless of existing knowledge of an SNP's functionality or biological plausibility of association. Because many tests are conducted, very low statistical significance thresholds (P < 5 × 10(-8)) are required to identify true associations with confidence. By restricting GWA analyses to SNPs with enhanced prior probabilities of association, we can reduce the number of tests conducted and relax the required significance threshold, increasing power to detect association. In this analysis of existing GWA data on pancreatic cancer cases (n = 1,736) and controls (n = 1,802) of European descent (the PanScan study), we conduct a GWA scan restricted to SNPs that have been reported to associate with human phenotypes in previous GWA studies (with P < 5 × 10(-8)). Using this method, we drastically reduce the number of tests conducted (from ~550,000 to 1,087) and test only SNPs that are known to be (or tag) variants that influence human biological processes. Of the 1,087 SNPs tested, the strongest association observed was for HNF1A SNP rs7310409 (P = 3 × 10(-5); P(Bonferroni) = 0.03), an SNP known to associate with circulating C-reactive protein. This association was replicated in an independent sample of 1,094 cases and 1,165 controls (P = 0.02), producing a highly significant association in the combined data sets (P = 2 × 10(-6); P(Bonferroni) = 0.002). The HNF1A region also harbors variants that influence several human traits, including maturity-onset diabetes of the young, type 2 diabetes, low-density lipoprotein cholesterol, and N-glycan levels. This novel "pleiotropy scan" method may be useful for identifying susceptibility loci for other cancer phenotypes.
| S-EPMC3129443 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-06-12 | E-GEOD-44636 | biostudies-arrayexpress
Project description:DNA double‑strand break repair is critically involved in oxaliplatin resistance in pancreatic ductal adenocarcinoma (PDAC). Hepatocyte nuclear factor 1 homeobox A (HNF1A) has received increased attention regarding its role in cancer progression. The present study explored the role of HNF1A in oxaliplatin resistance in PDAC. The results revealed that HNF1A expression was negatively associated with oxaliplatin chemoresistance in PDAC tissues and cell lines. HNF1A inhibition promoted the proliferation, colony formation and stemness of PDAC cells, and suppressed their apoptosis. Furthermore, HNF1A inhibition switched nonhomologous end joining to homologous recombination, thereby enhancing genomic stability and oxaliplatin resistance. Mechanistically, HNF1A transcriptionally activates p53‑binding protein 1 (53BP1) expression by directly interacting with the 53BP1 promoter region. Upregulation of HNF1A and 53BP1 induced significant inhibition of PDAC growth and oxaliplatin resistance in patient‑derived PDAC xenograft models and orthotopic models. In conclusion, the findings of the present study suggested that HNF1A/53BP1 may be a promising PDAC therapeutic target for overcoming oxaliplatin resistance.
| S-EPMC9990585 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2012-11-21 | E-GEOD-42429 | biostudies-arrayexpress