Effect of DEN-induced liver cancer in wildtype and OTUD3 knockout mice
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ABSTRACT:
PROVIDER: PRJNA1107973 | ENA |
REPOSITORIES: ENA
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Project description:To further investigate gene expression in DEN-induced liver cancer in mice with Otud3 gene knockout, we employed RNA-seq profiling as a discovery platform to identify the pathways or biological processes potentially responsible for the occurrence of DEN-induced liver cancer in both wildtype and Otud3 knockout mice. Liver cancer tissues from Otud3 knockout mice and their littermates, with or without a 14-day-old DEN injection, were utilized as samples for analysis.
2024-07-10 | GSE266622 | GEO
Project description:To investigate the global function of Ftcd in the regulation of hepatocarcinonegesis, we established DEN-induced or untreated liver-specific Ftcd knockout(referred as Ftcd LKO) murine model in which Ftcd has been knocked out by loxp/alb-cre system, take the wildtype(referred as WT) mice as control. We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different Ftcd LKO mice and 6 different WT mice at 12 months after DEN treatment, as well as RNA-seq of 3 different 12-month-old Ftcd LKO and WT mice.
2023-05-01 | GSE201454 | GEO
Project description:RNA-seq was performed on mRNA samples purified from the liver of wildtype (WT) and Sesn3 knockout (KO) mice.
2020-12-30 | GSE133441 | GEO
Project description:HGF has been reported to have both positive and negative effects on carcinogenesis. Here we show that the loss of c-Met signaling in hepatocytes enhanced rather than suppressed the early stages of chemical hepatocarcinogenesis. c-Met conditional knockout mice (c-metfl/fl, AlbCre+/-; MetLivKO) treated with N-nitrosodiethylamine (DEN) developed significantly more and bigger tumors and with a shorter latency as compared with control (wt/wt, AlbCre+/-; Cre-Ctrl) mice. Accelerated tumor development was associated with increased rate of cell proliferation and prolonged activation of epidermal growth factor receptor (EGFR) signaling. MetLivKO livers treated with DEN also displayed elevated lipid peroxidation, decreased ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG), and upregulation of superoxide dismutase 1 (Sod1) and heat shock protein 70 (Hsp70), all consistent with increased oxidative stress. Likewise, gene expression profiling performed at 3 and 5 months after DEN treatment revealed upregulation of genes associated with cell proliferation and stress responses in c-Met mutant livers. The negative effects of c-Met-deficiency were reversed by chronic oral administration of anti-oxidant N-acetylcysteine (NAC). NAC blocked the EGFR activation and reduced the DEN-initiated hepatocarcinogenesis to the levels of Cre-Ctrl mice. These results argue that intact HGF/c-Met signaling is essential for maintaining normal redox homeostasis in the liver and has tumor suppressor effect(s) during the early stages of DEN-induced hepatocarcinogenesis. Keywords: compound treatment design
2008-08-09 | GSE8747 | GEO
Project description:HGF has been reported to have both positive and negative effects on carcinogenesis. Here we show that the loss of c-Met signaling in hepatocytes enhanced rather than suppressed the early stages of chemical hepatocarcinogenesis. c-Met conditional knockout mice (c-metfl/fl, AlbCre+/-; MetLivKO) treated with N-nitrosodiethylamine (DEN) developed significantly more and bigger tumors and with a shorter latency as compared with control (wt/wt, AlbCre+/-; Cre-Ctrl) mice. Accelerated tumor development was associated with increased rate of cell proliferation and prolonged activation of epidermal growth factor receptor (EGFR) signaling. MetLivKO livers treated with DEN also displayed elevated lipid peroxidation, decreased ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG), and upregulation of superoxide dismutase 1 (Sod1) and heat shock protein 70 (Hsp70), all consistent with increased oxidative stress. Likewise, gene expression profiling performed at 3 and 5 months after DEN treatment revealed upregulation of genes associated with cell proliferation and stress responses in c-Met mutant livers. The negative effects of c-Met-deficiency were reversed by chronic oral administration of anti-oxidant N-acetylcysteine (NAC). NAC blocked the EGFR activation and reduced the DEN-initiated hepatocarcinogenesis to the levels of Cre-Ctrl mice. These results argue that intact HGF/c-Met signaling is essential for maintaining normal redox homeostasis in the liver and has tumor suppressor effect(s) during the early stages of DEN-induced hepatocarcinogenesis. Keywords: compound treatment design To address a role for c-Met in liver carcinogenesis, we employed a hepatocyte specific c-Met conditional knockout mouse model generated in our laboratory. Mice received a single intraperitoneal injection of 10 µg/g body weight of N-nitrosodiethylamine (DEN) (Sigma-Aldrich, Inc., St. Louis, MO, USA) at 14 days of age. Livers were examined at 3 and 5 months after DEN injection. Expression profiling was conducted on five animals from each genotype per time point. Total RNA pooled from five wild-type B6/129 strain mouse livers was used as universal hybridization reference. All experiments were performed in duplicates following a dye-swapping design. Arrays were scanned with a GenePix 4000A scanner (Axon Instruments Ltd., Burlingame, CA) in a way to achieve optimal signal intensity at both channels with less than 1% saturated spots. After excluding the invalid features, all arrays were normalized to the 50th percentile of the median signal intensity using the mAdb data analysis suite (http://nciarray.nci.nih.gov/). Unsupervised cluster analysis was performed with the Cluster and TreeView programs (http://rana.lbl.gov/EisenSoftware.htm). The BRB ArrayTools V3.3.0 software package (Biometric Research Branch, National Cancer Institute; http://linus.nci.nih.gov/BRB-ArrayTools.html) was used for the supervised comparison. Differentially expressed genes were selected using a univariate 2-sample t-test (P<0.001) with a random variance model (15). Functional classification of the significant genes was based on the Gene Ontology (GO) annotations (www.geneontology.org).
2008-08-09 | E-GEOD-8747 | biostudies-arrayexpress
Project description:In situ synthesized oligo arrays, U74Av2, from Affymetrix were used to measure differential gene expression in RNA samples generated from the liver of Nrf2 knockout and wildtype mice at 5 month age. Total RNAs from two Nrf2 knockout or wildtype littermates were analyzed separately. There are two replicates (GSM 13431, 13435) for the female Nrf2 wildtype group, two replicates (GSM 13439, 13441) for the male Nrf2 wildtype group, two replicates (GSM 13436, 13437) for the female Nrf2 knockout group, and two replicates (GSM 13438, 13440) for the male Nrf2 knockout group. Keywords: parallel sample
2003-12-16 | GSE864 | GEO
Project description:Transcriptomic analysis of hepatic genes in DEN-treated wildtype and Sesn3 knockout mice
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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:To investigate the SIX1 S225K-regulated gene compared SIX1 in DEN induced tumor in the liver specific knockin mice
2024-02-07 | GSE254929 | GEO
Project description:Using RNA-seq analysis, we study a DEN-induced HCC rat model during fibrosis progression and HCC development with special focus on liver inflammatory microenvironment. RNA-seq results show that DEN-induced liver tumors in rat model share remarkable molecular characteristics with human HCC, especially with HCC associated with high proliferation. In conclusion, our study provides detailed insight into the hepatocarcinogenesis in a commonly used model of HCC, facilitating the future use of this model for preclinical testing.
2021-10-08 | GSE182860 | GEO