Transient transfection of activated Notch1 (Notch1-ICD) decreases cellular proliferation and reduces the expression of a subset of neuroendocrine genes.
Comprehensive genomic profiles of small cell lung cancer.
Specimen part, Cell line, Time
View SamplesNotch intracellular domain (NICD) is the active form of the Notch receptor. In this mouse model, NICD is inserted in the Rosa26 locus downstream of a loxP-STOP-LoxP (lsl) sequence and therefore NICD expression is dependant on Cre recombinase expression. These mice are crossed with the AFP-Cre strain that expresses Cre in hepatoblasts due to its regulation by the AFP promoter and albumin enhancer. Mice from 6 to 12 months are sacrificed and liver RNA samples from control monotransgenic Rosa26-lsl-NICD and confirmed HCC lesions from bitransgenic AFP-Cre/Rosa26-lsl-NICD (AFP-NICD) are obtained. Exon expression profiling of these samples are submitted.
Notch signaling is activated in human hepatocellular carcinoma and induces tumor formation in mice.
Age, Specimen part
View SamplesGene expression profiles of 75 tissue samples were analyzed representing the stepwise carcinogenic process from pre-neoplastic lesions (cirrhosis and dysplasia) to HCC, including four neoplastic stages (very early HCC to metastatic tumors) from patients with HCV infection. Gene signatures that accurately reflect the pathological progression of disease at each stage were identified and potential molecular markers for early diagnosis uncovered. Pathway analysis revealed dysregulation of the Notch and Toll-like receptor pathways in cirrhosis, followed by deregulation of several components of the Jak/STAT pathway in early carcinogenesis, then up-regulation of genes involved in DNA replication and repair and cell cycle in late cancerous stages.
Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene-expression signature of vascular invasion in hepatocellular carcinoma.
Sex, Age, Specimen part
View SamplesUHRF1 is an essential regulator of DNA methylation that is highly expressed in many cancers. Using transgenic zebrafish, cultured cells and human tumors, we demonstrate that UHRF1 is an oncogene. RNAseq was used to assess the variation in gene expression between control and experimental samples. Overall design: Total small RNA from 2 batches of Tg(fabp10:has.UHRF1-GFP)High and age matched Tg(fabp10:nls-mCherry) control 5 dpf zebrafish livers was purified for preparation of high-throughput sequencing libraries.
UHRF1 overexpression drives DNA hypomethylation and hepatocellular carcinoma.
No sample metadata fields
View SamplesHere we study the adult functions of the single Drosophila member of this subfamily, DHR78, with the goal of defining its ancestral functions in the absence of genetic redundancy. We show that DHR78 mutants have a shortened lifespan and reduced motility. Mated DHR78 mutant females display reduced triglycerides along with a reduced feeding rate. Transcriptional profiling reveals a major role for DHR78 in promoting the expression of genes that are abundantly expressed in the midgut, suggesting that it contributes to nutrient uptake. We also identify roles for DHR78 in maintaining the expression of genes in the ecdysone and Notch signaling pathways. Overall design: Comparison of the transcriptional profile of DHR78-transheterozygote female mutants in a btl>DHR78 background with genetically matched controls
Adult functions for the Drosophila DHR78 nuclear receptor.
Sex, Age, Specimen part, Subject
View SamplesAlthough SIRT1 plays a central role in maintaining metabolic homeostasis, the molecular mechanisms remain unclear. Here we show that loss of the Drosophila SIRT1 homolog sir2 leads to the progressive onset of diabetic phenotypes, similar to studies of SIRT1 in mice. Sir2 function is both necessary and sufficient in the fat body to maintain peripheral insulin sensitivity. This activity is mediated by the Drosophila HNF4 nuclear receptor, which is deacetylated and stabilized through protein interactions with Sir2. This study demonstrates that the key metabolic activities of SIRT1 have been conserved through evolution and establishes HNF4 as a critical downstream target. Overall design: 4 sir2 mutant, 4 control samples, independent biological replicates
Sir2 Acts through Hepatocyte Nuclear Factor 4 to maintain insulin Signaling and Metabolic Homeostasis in Drosophila.
Age, Subject
View SamplesThere is a good deal of indirect evidence that improved insulin sensitivity may contribute to improved lifespan of mice in which aging has been slowed by mutations, drugs, or dietary means, even in stocks of mice that do not show signs of late-life diabetes. Peripheral responses to insulin can be augmented by over-expression of Syntaxin 4 (Syn4), a membrane SNARE protein. We show here that Syn4 transgenic (Tg) mice live approximately 33% longer than controls, and show increased peripheral insulin sensitivity, even at ages where controls show age-related insulin resistance. Hence, presumably Syn4 Tg mice spend more hours of each day under normoglycemic conditions, which may slow multiple aspects of aging and thereby extend lifespan, even in non-diabetic mice.
Syntaxin 4 Overexpression Ameliorates Effects of Aging and High-Fat Diet on Glucose Control and Extends Lifespan.
Sex, Specimen part
View SamplesHepatocellular carcinoma (HCC) is a complex and heterogeneous tumor due to activation of multiple cellular pathways and molecular alterations. Herein, we report the first molecular classification of 89 HCC based on the expression of 358 microRNAs and integrative genomic analysis. Three main subclasses of HCC were identified : two of them were associated with beta-catenin mutations or aggressive phenotype. A subset of the subclass of aggressive tumors (8/89, 9%) showed overexpression of a cluster of microRNAs located on chr19q13.41 (C19MC locus. We showed that miR 517a, representing C19MC, promoted cell proliferation, migration and invasion in vitro and induced the development of aggressive tumors in vivo suggesting its role as a novel oncogenic driver in HCC.
MicroRNA-based classification of hepatocellular carcinoma and oncogenic role of miR-517a.
Sex, Age, Specimen part
View SamplesmRNA expression profile modified by stable transfection of microRNA mir-517a (MIR517A) in a human hepatocellular carcinoma cell line Huh-7
MicroRNA-based classification of hepatocellular carcinoma and oncogenic role of miR-517a.
No sample metadata fields
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