Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA325326 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: CUGBP1 is an important regulator of liver homeostasis, through splicing regulation, stability, and mRNA translation. To aim to characterize the transcriptome of DEN-mediated liver cancer in CUGBP1 knock-in mice with Ser302 mutated to Ala (which mimics unphosphorylated CUGBP1 isoform) through RNA sequencing. Specifically, we compared gene expression levels to identify the impact of DEN-driven activation in both wildtype and CUGBP1 Ser302-to-Ala knock-in mice, focusing on downstream CUGBP1 targets and tumor activating pathways. Methods: Hepatic mRNA profiles were obtained through RNA sequencing of flash-frozen samples obtained at time of sacrifice. Results: We observe an augmentation of up- and downregulated cancer-related genes and pathways in CUGBP1 s302a knock-in mice compared to WT mice. We observe not only changes in expression related to oncogenesis, but also in splicing. Reduction of CUGBP1 protein due to the s302a variant leads to higher sensitivity to the development of liver cancer as a result of alterations in expression of down-stream mRNAs at both the splicing and expression levels. Conclusion: CUGBP1 is a strong tumor suppressor in the liver, and reduction of the CUGBP1 protein accelerates the development of liver cancer.
2017-06-12 | GSE83240 | GEO
Project description:Hepatocellular carcinoma is the third leading cause of cancer death worldwide, and it is necessary to elucidate the mechanism of hepatocarcinogenesis. Hepatocellular carcinoma (HCC) has a high mortality rate and develops based on the chronic inflammatory hepatic disease. Therefore, novel prophylactic or therapeutic strategies are required to improve outcome. In this study, influence of diethylnitrosamine (DEN) and retinoic acid (ATRA) on hepatocarcinogenesis was investigated in mouse. These results suggest that the control of NF-M-NM-:B signaling during the early stage of HCC development is important for the prevention of malignant transformation in hepatocytes. Genes induced by the following treatments in mice liver were investigated at 2 days or 7 days after treatment; DEN: diethylnitrosamine (treatment of DEN (drinking water 80 mg/L)) ATRA: retinoic acid (treatment of ATRA (drinking water 30 mg/L)) G0s2 siRNA : G0s2 knockdown mouse liver (treatment of G0s2 siRNA) Control siRNA: treatment of scramble siRNA (negative control)
2014-06-06 | E-GEOD-57798 | biostudies-arrayexpress
Project description:Non-alcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) is a significant risk factor for hepatocellular carcinoma (HCC). However, a preclinical model of progressive NAFLD/NASH is largely lacking. Here, we report that mice with hepatocyte-specific deletion of Tid1, encoding a mitochondrial cochaperone, tended to develop NASH-dependent HCC. Mice with hepatic Tid1 deficiency showed impairing mitochondrial function and causing fatty acid metabolic dysregulation; meanwhile, sequentially developed fatty liver, NASH, and cirrhosis/HCC in a diethylnitrosamine (DEN) induced oxidative environment. The pathological signatures of human NASH, including cholesterol accumulation and activation of inflammatory and apoptotic signaling pathways, are also present in these mice. Clinically, low Tid1 expression was associated with unfavorable prognosis in patients with HCC. Empirically, hepatic Tid1 deficiency directly disrupts entire mitochondria that play a key role in the NASH-dependent HCC development. Overall, we established a new mouse model that develops NASH-dependent HCC and provides a promising approach to improve the treatment.
2022-06-02 | E-MTAB-9973 | biostudies-arrayexpress
Project description:In our current study, we observed that in hepatic carcinogen diethylnitrosamine (DEN)-induced liver tumor mouse model, diphthamide-deficient mouse developed less liver tumor incidence than control mouse. To explore the detailed mechanism, RNA-seq experiment was conducted to compare gene transcriptome profiles of control and diphthamide-deficient livers during HCC progression.
2021-12-21 | GSE191192 | GEO
Project description:Gene-expression profiles of rat hepatocellular carcinoma induced by diethylnitrosamine (DEN) and the effect of erlotinib Hepatocellular carcinoma (HCC) is the sixth most common solid tumor worldwide and the third leading cause of cancer-related death. Given the lack of successful treatment options, chemoprevention in high-risk patients has been proposed as an alternative strategy. Mounting evidence supports a role for epidermal growth factor (EGF) during chronic liver disease and hepatocellular transformation. We address the hypothesis that blocking the EGF-EGF receptor (EGFR) pathway may be an effective strategy for inhibiting fibrogenesis and hepatocarcinogenesis. A rat model of diethylnitrosamine (DEN)-induced cirrhosis was used to examine the effects of erlotinib on underlying chronic liver disease and HCC formation. The DEN-induced rat model closely resembles disease progression in humans both pathologically and molecularly. Erlotinib significantly prevented the development of HCC tumor nodules in a dose-dependent fashion. Further, erlotinib inhibited the activation of hepatic stellate cells and prevented fibrogenesis. Erlotinib also reduced hepatotoxicity and improved liver function. Finally, a gene expression signature predictive of poor survival in human cirrhosis patients was reversed in response to erlotinib. Our data demonstrate for the first time that EGFR inhibition prevents liver fibrogenesis. Further, our results suggest that erlotinib is a potentially effective HCC chemoprevention strategy through inhibition of cirrhosis progression which can be monitored at the molecular level.
2014-02-28 | GSE27638 | GEO
Project description:Male rats received repeated low-dose diethylnitrosamine (DEN) to induce liver cirrhosis, and were treated with nizatidine to examine change of liver transcriptome and its association with liver cancer chemopreventive effect of nizatidine.
2021-06-28 | GSE115473 | GEO
Project description:Genetic polymorphisms that impair VLDL secretion are linked to hepatic steatosis, fibrosis and hepatocellular cancer (HCC). Liver-specific deletion of microsomal triglyceride transfer protein (Mttp-LKO) impairs VLDL assembly, promoting hepatic steatosis and fibrosis, which are attenuated in Mttp-LKO mice with germline Fabp1 deletion (Fabp1/Mttp DKO) mice. Here we examine the impact of impaired VLDL secretion in Mttp-LKO mice on HCC incidence and progression in comparison to Fabp1/Mttp DKO mice. DEN treated Mttp-LKO mice exhibited steatosis with increased tumor burden compared to flox controls, while diethylnitrosamine (DEN)- treated Fabp1/Mttp DKO mice exhibited a paradoxical increase in tumor burden and >50% mortality by 50 weeks. Lipidomic surveys revealed progressive enrichment in distinct triglyceride species in livers from Mttp-LKO mice with further enrichment in Fabp1/Mttp DKO mice. RNAseq analysis performed on liver tissue at 6 months revealed mRNA changes suggesting altered monocarboxylic acid utilization and increased aerobic glycolysis, while hepatocytes from Fabp1/Mttp DKO mice exhibited increased capacity to utilize glucose and glutamine. Taken together, these findings demonstrate that hepatic tumorigenesis is increased in mice with impaired VLDL secretion and further accelerated via pathways including altered fatty acid compartmentalization and shifts in hepatic energy utilization.
2024-02-12 | GSE253701 | GEO
Project description:Gene expression profiling was performed in each of hepatocyte fraction and non-parenchymal cell fraction enriched with activated hepatic stellate cells/myofibroblasts from cirrhotic rat livers induced by repeated, low-dose diethylnitrosamine (DEN) treatment.
2016-12-16 | GSE63726 | GEO
Project description:Gene-expression profiles of rat liver cirrhosis induced by diethylnitrosamine and the effect of erlotinib on liver fibrogenesis and liver cancer development Hepatocellular carcinoma (HCC) is the sixth most common solid tumor worldwide and the third leading cause of cancer-related death. Given the lack of successful treatment options, chemoprevention in high-risk patients has been proposed as an alternative strategy. Mounting evidence supports a role for epidermal growth factor (EGF) during chronic liver disease and hepatocellular transformation. We address the hypothesis that blocking the EGF-EGF receptor (EGFR) pathway may be an effective strategy for inhibiting fibrogenesis and hepatocarcinogenesis. A rat model of diethylnitrosamine (DEN)-induced cirrhosis was used to examine the effects of erlotinib on underlying chronic liver disease and HCC formation. The DEN-induced rat model closely resembles disease progression in humans both pathologically and molecularly. Erlotinib significantly prevented the development of HCC tumor nodules in a dose-dependent fashion. Further, erlotinib inhibited the activation of hepatic stellate cells and prevented fibrogenesis. Erlotinib also reduced hepatotoxicity and improved liver function. Finally, a gene expression signature predictive of poor survival in human cirrhosis patients was reversed in response to erlotinib. Our data demonstrate for the first time that EGFR inhibition prevents liver fibrogenesis. Further, our results suggest that erlotinib is a potentially effective HCC chemoprevention strategy through inhibition of cirrhosis progression which can be monitored at the molecular level. Keywords: Cirrhotic liver, Expression array, Illumina, Signatures, Outcome prediction
2014-02-28 | GSE19057 | GEO
Project description:We used microarrays to detail the molecular mechanism underlying the HLF (hepatic leukemia factor)-triggered HCC (hepatocellular carcinoma) initiation We conducted transcriptome microarray analysis of DEN (diethylnitrosamine)-induced HCCs from HLF-deficient mice or WT (wild type) mice.
2019-02-01 | GSE125934 | GEO