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

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

PROVIDER: PRJNA659367 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12515014.fastq.gz	Fastqsanger.gz
	SRR12515015.fastq.gz	Fastqsanger.gz
	SRR12515016.fastq.gz	Fastqsanger.gz
	SRR12515017.fastq.gz	Fastqsanger.gz
	SRR12515018.fastq.gz	Fastqsanger.gz

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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.

2022-03-02 | GSE156849 | GEO

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

Project description:Obesity-induced metabolic dysfunction-associated steatohepatitis (MASH) leads to hepatocellular carcinoma (HCC). Astrocyte-elevated gene-1/Metadherin (AEG-1/MTDH) plays a key role in promoting MASH and HCC. AEG-1 is palmitoylated at residue cysteine 75 (Cys75) and a knock-in mouse representing mutated Cys75 to serine (AEG-1-C75S) showed activation of MASH- and HCC-promoting gene signature when compared to wild-type littermates (AEG-1-WT). The liver consists of 3 zones, periportal, midlobular and pericentral, and zone-specific dysregulated gene expression impairs metabolic homeostasis in the liver, contributing to MASH and HCC. Here, to elucidate how palmitoylation influences AEG-1-mediated gene regulation in regards to hepatic zonation, we performed spatial transcriptomics (ST) in the livers of AEG-1-WT and AEG-1-C75S littermates.

2024-06-05 | GSE261057 | GEO

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.

2012-07-24 | E-GEOD-34669 | biostudies-arrayexpress

AEG-1 silencing induced gene expression alteration in glioma cells

2011-07-12 | GSE29952 | GEO

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

Expression data from AEG-1fl/fl and AEG-1DHEP mice which have conditional hepatocyte-specific knockout 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 conditional hepatocyte-specific knockout mouse was generated by crossing floxed AEG-1 mouse with Alb/Cre mouse in C57BL/6 background

2017-08-02 | GSE85098 | GEO

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

2014-09-30 | GSE61875 | GEO

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

2012-07-25 | GSE34669 | GEO

AEG-1 silencing induced gene expression alteration in glioma cells

Project description:This experiment is designed to evaluate gene expression alteration following AEG-1 (MTDH) silencing in glioma cells. AEG-1 is found to be a potential regulator through interaction with other transcription factor. We intended to investigate the enriched transcription factor dependent downstream gene sets regulated by AEG-1 form the differential expressed genes we obtained from AEG-1 silencing. Total RNA were extracted from U87MG glioma cells stably silencing AEG-1 and correspondent pSuper Retro vector cells respectively. Passage 5 of the indicated cells after infection and selection were harvested for RNA extraction.

2011-07-12 | E-GEOD-29952 | biostudies-arrayexpress

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.

2013-07-01 | E-GEOD-46701 | biostudies-arrayexpress

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