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Mechanisms of AICAR in lung cancer

ABSTRACT: The purpose of the research is to delineate the mechanism behind AICAR-induced cytotoxicity by understanding the genetic pathways that are affected with AICAR treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE198777 | GEO | 2023/02/21

REPOSITORIES: GEO

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Effect of AICAR monophosphate and AICAr riboside accumulation on global transcription

Project description:AICAR monophosphate (5-Aminoimidazole-4-carboxamide ribonucleotide) is a metabolic intermediate of the de novo purine synthesis pathway presenting highly promising metabolic and antiproliferative properties. Yeast mutants accumulating AICAR are auxotroph for histidine. A screening for suppressors of this phenotype identified recessive and dominant mutants that result in lowering intracellular AICAR concentration. The recessive mutants affect adenosine kinase which is shown here to catalyze the phosphorylation of AICAR riboside in yeast. The dominant mutants strongly enhance the capacity of the alkaline phosphatase Pho13p to dephosphorylate succinyl-AICAR monophosphate into the non-toxic riboside form. By combining these mutants to transcriptomic and metabolomic analyses, we establish that in yeast both toxic and physiological responses to AICAR are linked to the concentration of the monophosphate form, while the nucleoside moiety has no effect even at high concentration. Finally, we establish that (S)AICAR concentration varies under physiological conditions, thus modulating transcriptional regulation of purine pathway genes. This SuperSeries is composed of the SubSeries listed below.

2011-07-11 | GSE29324 | GEO

AICAR regulate IEGs expression in ALL cells

Project description:To identify genes transcriptionally regulated by AICAR under cellular stress, We treated NALM6 cells for 45 min with vehicle (DMSO) or AICAR (15 mM), and examined their RNA profile using RNA-Seq. The immediate early genes (IEGs) were identified as a subset of genes downregulated by AICAR.

2021-07-22 | GSE152917 | GEO

Identifying CHIR99021 and AICAR-regulated genes in the J1 mESCs

Project description:It has been demonstrated that CHIR99021 promotes self-renewal of mouse embryonic stem cells, however, the target genes of CHIR99021 is not fully understood. AICAR is the activator of AMP-activated protein kinase. It is reported that AICAR plays important role in mouse embryonic stem cells, however the moleculor mechanism of this phenomenon is unknown. To better understand the downstream target genes of CHIR99021 and AICAR, we performed Microarray analyses to identify their downstream targets. The data show the genes regulated by CHIR99021 or AICAR.

2013-01-01 | GSE40959 | GEO

RNA-seq of U937 cells treated with AICAr

Project description:U937 cells were treated wth 0.2 mM AICAr for 24 h to compare the results on cell line know to differentiate in the presence of AICAr with the results on primary patient sample.

2020-11-15 | E-MTAB-9537 | biostudies-arrayexpress

Identifying CHIR99021 and AICAR-regulated genes in the J1 mESCs

2013-01-01 | E-GEOD-40959 | biostudies-arrayexpress

AICAR can modulate the expression of microRNA in J1 mESC

Project description:We have demonstrated AICAR can maintain J1 mouse ES cells pluripotency in our previous research, yet its effects on ES cells miRNAs expression remain a mystery. In this study, we performed small RNA (sRNA) High-throughput sequencing using Illumina HiSeq 2000 to investigate the influence of AICAR on J1 mouse ES cells miRNAs expression and further found the mechanism of how miRNAs affect ES cells pluripotency maintenance. Samples that treated by DMSO is used as a control. Compare microRNA expression of J1 mESC cultured with or without small molecule AICAR

2014-02-06 | E-GEOD-54586 | biostudies-arrayexpress

Role of Ado1p in the transcriptional response associated with AICAr supplementation

Project description:We investigated the role of Ado1p associated with AICAr supplementation on the global transcriptome of Y3188. The Y3188 strain was grown with or without AICAr. For each comparison, we made 2 biological replicates, swapping dyes.

2011-08-31 | E-GEOD-29020 | biostudies-arrayexpress

Effect of AICAR and SAICAR accumulation on global transcription (second part)

Project description:We investigated the effects of AICAR and SAICAR accumulation on transcriptional regulation of purine biosynthesis and other metabolic pathways. These data were compared to those obtained in the ade16ade17 vs WT data set to determine the transcriptional effects associated to AICAR/SAICAR accumulation and those due to ade16 and ade17 deletions. In this work, global transcription analyses were combined to measurements of intracellular nucleotides pools by HPLC Keywords: Comparative genomic transcription analysis on total RNA from cells accumulating or lacking AICAR and SAICAR nucleotide derivatives.

2009-05-15 | GSE13183 | GEO

Effect of 5-amino-4-imidazolecarboxamide ribotide (AICAr) supplementation on global transcription

Project description:We investigated the effects of AICAr supplementation on the global transcriptome of Y2950. The Y2950 strain was grown with or without AICAr. For each comparison, we made 2 biological replicates, swapping dyes.

2011-08-31 | E-GEOD-29019 | biostudies-arrayexpress

Expression data from AMPKalpha1/2-double knockout murine embryonic fibroblasts stimulated or not with AICAR

Project description:AICAR is a metabolite with anti-tumoral properties. Its monophosphate derivative ZMP is an AMP mimetic activator of the protein kinases AMPK. However, AICAR also mediates AMPK-independent effects. A kinetic transcriptome analysis was therefore carried out in Ampkα1/α2 double knockout murine embryonic fibroblasts in response to AICAR in order to unveil these AMPK-independent functions,

2018-05-31 | GSE106460 | GEO

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