Expression data for murine hepatocellular carcinoma in WT and Top1mt-/- mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE122489 | GEO | 2018/11/14
REPOSITORIES: GEO
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Project description:Due to the global obesity epidemic the incidences of nonalcoholic steatohepatitis (NASH) and NASH-related hepatocellular carcinoma (HCC) are on the rise. Non-invasive treatment options for HCC are scarce and innovative therapy regimes are urgently needed. The mechanistic target of rapamycin (mTOR) is of fundamental importance for the regulation of cellular metabolism and mTOR pathway activation is frequently observed in HCCs. However, mTOR inhibition failed to benefit the clinical course of HCC patients, demonstrating the need for a better understanding of the molecular and functional consequences of blocking mTOR signaling in primary liver cancer. To address this, we established a tumor cell-specific inactivation of mTOR in a murine model of non-alcoholic steatohepatitis (NASH)-driven HCC. After 30 weeks of diet, tumor, and liver volumes as well as whole body fat percentage were evaluated by non-invasive in vivo micro-computed tomography (µCT), and livers were collected for subsequent analyses. Unexpectedly, the tumor load exploded in mTORLEC livers and knock-out mice showed improved glucose tolerance among other signs of major metabolic alterations. Detailed proteome analysis indicated extensive changes in arachidonic and bile acid metabolism in the liver. The simulation of metformin intervention via kinetic modeling predicted the existence of a therapeutic window, in which the drug selectively targets mTORLEC HCC tissue.
2023-11-15 | PXD039944 | Pride
Project description:<p>Despite the growing incidence of hepatocellular carcinoma (HCC) due to increased hepatitis C virus infection and non-alcoholic steatohepatitis in Western populations, the genetic determinants of this cancer have yet to be established. A minority (15-20%) of HCC occurs in livers without cirrhosis or other chronic disease. Because the liver is functionally preserved in these patients and surgical resection of the tumor may be performed safely, and because of the scarcity of livers available for transplantation, non-cirrhotic patients undergo surgical resection for HCC treatment. These resected tumors present investigatory opportunities in two ways: First, they provide tumor specimen which have not been treated with chemotherapy and embolization. Second, the absence of cirrhosis may provide an unconfounded background from which to investigate the genetic tumorigenesis of HCC. In livers with cirrhosis, genetic instability is prevalent as assessed by assays for microsatellite instability, loss of heterozygosity and aberrant DNA methylation. In contrast, in livers without cirrhosis, the non-tumor tissue surrounding HCC have been found to have fewer genetic aberrations. It has been postulated that the pathologic process of cirrhosis may result in the accumulation of many "passenger"; as well as "driver" mutations, and that the examination of the HCC cancer genome may be facilitated in non-cirrhotic livers because of the absence of an accumulated background noise of mutations.</p>
| phs001106 | dbGaP
Project description:Whole body knockout mice lacking IQ-motif containing GTPase-activating protein 2 (IQGAP2) develop spontaneous hepatocellular carcinoma (HCC) at the age of 12 months and older (Schmidt et al., 2008). Hepatic transcript expression profiles were obtained for IQGAP2 knockout and wild-type control mice of two age groups, 6- and 24-month-old. Liver samples from 24-month-old IQGAP2 knockout mice were HCC tumors, livers from all other groups were tumor-free. Results provide insights into the potential role of IQGAP2 as a liver-specific tumor suppressor. Transcript profiles of four groups of mouse livers (N = 3 in each group) were compared using Affymetrix GeneChip® Mouse Genome 430 2.0 Array. The groups included livers from 6- and 24-month-old wild-type (WT) mice and 6- and 24-month-old (KO) Iqgap2-/- mice.
2013-12-13 | E-GEOD-46646 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) remains a major health problem worldwide, and HCC patients have a poor prognostic outcome. In this study, we systematically disclose mechanisms of hepatocarcinogenesis, and also effectively identify and validate novel anticancer targets in HCCs. Keywords: disease state analysis total 58 cDNA microarrays, all experiment samples are hepatocellular carcinoma. RNAs from 33 corresponding noncancerous livers and 5 normal livers were used as the reference, respectively. The tumor samples were labeled with Cy5-dUTP.The nontumor samples were labeled with Cy3-dUTP.
2009-01-06 | E-GEOD-4108 | biostudies-arrayexpress
Project description:aCGH analysis of murine transgenic liver tissues affected with HCC, hybridized with age (18 months) and sex matched C57BL/6 mice. Moreover, 18months old C57BL/6 livers were hybridized with independent 18 months old C57BL/6 livers for control. Keywords: Array comparative genomic hybridization analysis (aCGH). Independent HCC of AlbLTab mice were hybridized with independent C57BL/6 mice.
2010-05-15 | E-GEOD-14467 | biostudies-arrayexpress
Project description:Expression data for murine hepatocellular carcinoma in WT and Top1mt-/- mice
| PRJNA505344 | ENA
Project description:We used doxycycline (dox) treatment to generate a larval model of hepatocellular carcinoma (HCC)22. In this model, we induced the expression of a single EGFP-krasG12V transgene, denoted TO(krasG12V)T/+ in developing livers by treating with doxycycline between 2-7 days post-fertilisation (dpf). This led to the accumulation of a constitutively active, EGFP-tagged, potently oncogenic form of Kras specifically in hepatocytes, causing hepatocyte hyperplasia and a substantial increase in total liver volume. We used RNA sequencing to analyse the gene expression patterns of hepatocytes expressing the krasG12V transgene compared to wildtype (WT) livers expressing no transgene. We detected more than 6000 significantly upregulated genes in dox-treated TO(krasG12V)T/+ livers compared WT livers, and a further 6000+ genes were significantly downregulated. Of the upregulated genes, many were significantly enriched in KEGG pathways associated with highly proliferative cancers, including DNA replication, cell cycle and DNA damage repair. Geneset enrichment analysis identified a positive correlation between the differential gene expression data from the dox-treated TO(krasG12V)T/+ versus WT livers and the differential gene expression data for the HCC (LIHC) and healthy liver subsets available from The Cancer Genome Atlas. We also found a positive correlation between the DEGs from the dox-treated TO(krasG12V)T/+ versus WT livers and a small HCC expression signature based on four patient samples carrying KRAS G12 or KRAS G13 mutations. These observations build on previous reports that dox-treated TO(krasG12V)T/+ zebrafish provide an authentic model of human HCC.
2023-02-03 | GSE220282 | GEO
Project description:aCGH analysis of murine transgenic liver tissues affected with HCC, hybridized with age (18 months) and sex matched C57BL/6 mice. Moreover, 18months old C57BL/6 livers were hybridized with independent 18 months old C57BL/6 livers for control. Keywords: Array comparative genomic hybridization analysis (aCGH).
2009-07-29 | GSE14467 | GEO
Project description:As the central hub metabolic organ bodily, the liver is paramount to keep whole-body energy homeostasis. Further, mitochondria are the central metabolic hub within cells to connect the main catabolized, energy production, and hormonal signaling pathways. It is evident that mitochondrial dysfunction may play a critical role in the development of NASH. Accordingly, understanding the underlying mechanisms of mitochondrial dysfunction is of importance to develop therapies for NASH. Here, we report that mice with hepatocyte-specific deletion of Tid1, encoding a mitochondrial cochaperone, tended to develop NASH-dependent HCC. The hepatocellular nodules were developed in 3-month DEN-treated Tid1-/- mice. At the age of 6 months, the DEN-treated Tid1-/- mice showed a higher number of tumors and greater tumor size than the DEN-treated Tid1+/- mice, followed by the DEN-treated WT mice. To gain insights into the mRNA changes during NASH-HCC progress, we performed an RNA-seq analysis with livers collected from 6-month DEN-treated mice.
2022-07-02 | E-MTAB-9974 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) is frequently characterized by metabolic and immune remodeling in the tumor microenvironment. We previously discovered that liver-specific deletion of fructose-1, 6-bisphphotase 1 (FBP1), a gluconeogenic enzyme ubiquitously suppressed in HCC tissues, promotes liver tumorigenesis, and induces metabolic and immune perturbations closely resembling human HCC. However, the underlying mechanisms remain incompletely understood. Here we reported that FBP1-deficient livers exhibit diminished amounts of natural killer (NK) cells and accelerated tumorigenesis. Using the diethylnitrosamine-induced HCC mouse model, we analyzed potential changes in the immune cell populations purified from control and FBP1-depleted livers and found that NK cells were strongly suppressed. Mechanistically, FBP1 attenuation in hepatocytes derepresses an EZH2-dependent transcriptional program to inhibit PKLR expression. This leads to reduced levels of PKLR cargo proteins sorted into hepatocyte-derived EVs, dampened activity of EV-targeted NK cells, and accelerated liver tumorigenesis. Our study demonstrated that hepatic FBP1 depletion promotes HCC-associated immune remodeling, partly through the transfer of hepatocyte-secreted, PKLR-attenuated EVs to NK cells.
2023-03-11 | PXD026822 | Pride