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Expression data from AEG-1fl/fl and AEG-1DHEP mice which have conditional hepatocyte-specific knockout of AEG-1 (Astrocyte elevated gene 1)

ABSTRACT: AEG-1 is overexpressed in human hepatocellular carcinoma (HCC) and positively regulates development and progression of HCC A conditional hepatocyte-specific knockout mouse was generated by crossing floxed AEG-1 mouse with Alb/Cre mouse in C57BL/6 background

ORGANISM(S): Mus musculus

PROVIDER: GSE85098 | GEO | 2017/08/02

SECONDARY ACCESSION(S): PRJNA336171

REPOSITORIES: GEO

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Expression data from Wild-type (WT) and Alb/AEG-1 mice which are transgenic mice with hepatocyte-specific overexpression of AEG-1 (Astrocyte elevated gene 1)

Project description:AEG-1 is overexpressed in human hepatocellular carcinoma (HCC) and positively regulates development and progression of HCC A transgenic mouse with hepatocyte-specific expression of human AEG-1 was generated using mouse albumin promoter/enhancer in B6/CBA background. Hepatocytes were isolated from WT and Alb/AEG-1 mice for RNA extraction and Affymetrix microarray hybridization.

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Astrocyte elevated gene-1 (AEG-1) promotes hepatocarcinogenesis: novel insights from a mouse model

Project description:Astrocyte elevated gene-1 (AEG-1) as a positive inducer of hepatocellular carcinoma (HCC). Transgenic mice with hepatocyte-specific expression of AEG-1 were challenged with N-nitrosodiethylamine (DEN) and developed multinodular HCC with steatotic features. Thus, we have identified the follwoing AEG-1 functions: induction of steatosis, inhibition of senescence and activation of coagulation pathway to augment an aggressive hepatocarcinogenic phenotype. Transgenic Mice liver tumors compared against WT mice liver tumors.

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Expression data from Wild-type (WT) and Alb/AEG-1 mice which are transgenic mice with hepatocyte-specific overexpression of AEG-1 (Astrocyte elevated gene 1)

2013-07-01 | GSE46701 | GEO

Astrocyte elevated gene-1 (AEG-1) promotes hepatocarcinogenesis: novel insights from a mouse model

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Astrocyte elevated gene-1 (AEG-1) and c-Myc cooperate to promote hepatocarcinogenesis

Project description:Double transgenic mice with hepatocyte-specific expression of AEG-1 and c-Myc show aggressive HCC compared to single transgenics. Gene expression was analyzed to understand the molecular mechanism by which AEG-1 and c-Myc cooperate to promote hepatocarcinogenesis. Livers were collected from naïve adult mice (3 mice/group). Total RNA was extrancted and subjected to RNA-Seq.

2014-09-30 | E-GEOD-61875 | biostudies-arrayexpress

Astrocyte elevated gene-1 (AEG-1) and c-Myc cooperate to promote hepatocarcinogenesis

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Dissecting the Balance between Metabolic and Oncogenic Functions of Astrocyte Elevated Gene-1/Metadherin (AEG-1/MTDH)

Project description:Obesity is an enormous global health problem and obesity-induced non-alcoholic steatohepatitis (NASH) is contributing to a rising incidence and mortality for hepatocellular carcinoma (HCC). Increase in de novo lipogenesis (DNL) and decrease in fatty acid -oxidation (FAO) underlie hepatic lipid accumulation in NASH. Astrocyte elevated gene-1/metadherin (AEG-1/MTDH) overexpression contributes to both NASH and HCC. AEG-1 harbors an LXXLL motif through which it blocks activation of peroxisome proliferator activated receptor  (PPAR), a key regulator of FAO. To better understand the role of LXXLL motif in mediating AEG-1 function, using CRISPR/Cas9 technology, we have generated a novel mouse model (AEG-1-L24K/L25H) in which the LXXLL motif in AEG-1 was mutated to LXXKH. We observed increased activation of PPAR in AEG-1-L24K/L25H livers providing partial protection from high fat diet (HFD)-induced steatosis. Interestingly, even with equal gene dosage levels, compared to AEG-1-WT livers, AEG-1-L24K/L25H livers exhibited increase in levels of lipogenic enzymes, mitogenic activity and inflammation which are attributes observed when AEG-1 is overexpressed. These findings indicate that while LXXLL motif favors steatotic activity of AEG-1 it keeps in check inflammatory and oncogenic functions thus maintaining a homeostasis in AEG-1 function. Conclusion: AEG-1 is being increasingly appreciated as a viable target for ameliorating NASH and NASH-HCC and as such in-depth understanding of the functions and molecular attributes of this molecule is essential. The present studies unravel the unique role of the LXXLL motif in mediating the balance between the metabolic and oncogenic functions of AEG-1.

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Spatial Transcriptomics Unravels Palmitoylation and Zonation-Dependent Gene Regulation by AEG-1 in Mouse Liver

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Palmitoylation negatively regulates AEG-1 function

Project description:In vitro studies revealed that AEG-1 is palmitoylated at cysteine at a.a. 75 position. In order to check how palmitoylation regulates AEG-1 function in vivo we generated a knockin moue using CRISPR/Cas9 taking in which cysteine 75 was mutated to serine (AEG-1-C75S). Hepatocytes were isolated from AEG-1-WT and AEG-1C75S littermates, total RNA was isolated and RNA-sequencing was performed.

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