Expression profile of GATA6 deficient pancreatic islets
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE106316 | GEO | 2019/10/31
REPOSITORIES: GEO
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Project description:Transcriptome analysis has uncovered a series of long noncoding RNAs (lncRNAs) transcribed during cell differentiation. Here, we uncovered lncRNA GATA6-AS1 is a functional lncRNA in definitive endoderm (DE) differentiation. We found GATA6-AS1 positively regulated the expression of endoderm key factor GATA6, which was different from previous reports in other biological contexts. Further investigation showed GATA6-AS1 interacted with SMAD2/3 and recruited SMAD2/3 to the promoter region of the GATA6 gene locus. In addition, overexpression of GATA6 was able to rescue the defect of DE differentiation due to the absence of GATA6-AS1, suggesting GATA6 was the functional target of GATA6-AS1 during endoderm differentiation. Ultimately, our study uncovers GATA6-AS1 is necessary for DE and pancreas differentiation, and reveals the detailed regulation mechanism between GATA6-AS1 and DE differentiation.
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Project description:Pancreatobiliary cancers have among the highest mortality rates of any cancer type. Discovering the full spectrum of molecular genetic alterations may suggest new avenues for therapy. To catalogue genomic alterations, we carried out array-based genomic profiling of 31 exocrine pancreatic cancers and 6 distal bile duct cancers, expanded as xenografts to enrich the tumor cell fraction. We identified numerous focal DNA amplifications and deletions, including in 19% of pancreatobiliary cases gain at cytoband 18q11.2, a locus uncommonly amplified in other tumor types. The smallest shared amplification at 18q11.2 included GATA6, a transcriptional regulator previously linked to normal pancreas development. When amplified, GATA6 was overexpressed at both the mRNA and protein level, and strong immunostaining was observed in 25 of 54 (46%) primary pancreatic cancers compared to 0 of 33 normal pancreas specimens surveyed. GATA6 expression in xenografts was associated with specific microarray gene-expression patterns, enriched for GATA binding sites and mitochondrial oxidative phosphorylation activity. siRNA mediated knockdown of GATA6 in pancreatic cancer cell lines with amplification led to reduced cell proliferation, cell cycle progression, and colony formation. Our findings indicate that GATA6 amplification and overexpression contribute to the oncogenic phenotypes of pancreatic cancer cells, and implicate GATA6 as a lineage-specific oncogene in pancreatobiliary cancer, with implications for novel treatment strategies. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Tissue type: cancer xenograft from diff tissues Keywords: Logical Set cDNA microarrays from the Stanford Functional Genomics Facility were used to perform gene expression profiling on 28 out of 31 of the exocrine pancreatic cancer and all 6 distal bile duct cancer xenografts. Using regression correlation
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Project description:Pancreatobiliary cancers have among the highest mortality rates of any cancer type. Discovering the full spectrum of molecular genetic alterations may suggest new avenues for therapy. To catalogue genomic alterations, we carried out array-based genomic profiling of 31 exocrine pancreatic cancers and 6 distal bile duct cancers, expanded as xenografts to enrich the tumor cell fraction. We identified numerous focal DNA amplifications and deletions, including in 19% of pancreatobiliary cases gain at cytoband 18q11.2, a locus uncommonly amplified in other tumor types. The smallest shared amplification at 18q11.2 included GATA6, a transcriptional regulator previously linked to normal pancreas development. When amplified, GATA6 was overexpressed at both the mRNA and protein level, and strong immunostaining was observed in 25 of 54 (46%) primary pancreatic cancers compared to 0 of 33 normal pancreas specimens surveyed. GATA6 expression in xenografts was associated with specific microarray gene-expression patterns, enriched for GATA binding sites and mitochondrial oxidative phosphorylation activity. siRNA mediated knockdown of GATA6 in pancreatic cancer cell lines with amplification led to reduced cell proliferation, cell cycle progression, and colony formation. Our findings indicate that GATA6 amplification and overexpression contribute to the oncogenic phenotypes of pancreatic cancer cells, and implicate GATA6 as a lineage-specific oncogene in pancreatobiliary cancer, with implications for novel treatment strategies. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Tissue type: cancer xenograft from diff tissues Keywords: Logical Set
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