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Expression data from human primary fibroblasts (IMR90) stably expressing H-RasV12 and treated with Metformin or vehicle

ABSTRACT: Metformin reduces the incidence of cancer in diabetics or in animal models. At the cellular level, the effects of metformin include the inhibition of complex I of the mitochondrial electron transport chain, a reduction in ATP levels and the activation of the energy sensor AMP kinase. Metformin also prevents the production of reactive oxygen species in primary human cells expressing oncogenic ras and the DNA damage associated to the process. We used microarrays to characterize the gene expression changes induced by metformin in primary human fibroblasts expressing oncogenic ras.

ORGANISM(S): Homo sapiens

PROVIDER: GSE33612 | GEO | 2013/04/01

SECONDARY ACCESSION(S): PRJNA148507

REPOSITORIES: GEO

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Expression data from human primary fibroblasts (IMR90) stably expressing H-RasV12 and shRNA against ERK2 or a non-targeting shRNA

Project description:Oncogenic ras activates several signaling pathways that cooperate in cell transformation. They include the ERK/MAP kinase pathway, the PI3K pathway and the Ral pathway among others. Surprisingly, in primary human fibroblasts, oncogenic ras expression induces senescence not transformation, but upon knockdown of ERK2 senescence is bypassed and transformation is stimulated. We used microarrays to characterize the gene expression programme of cells transformed by oncogenic ras, telomerase and knockdown of the ERK2 kinase. Primary human fibroblasts were co-infected with a retroviral vector that expresses oncogenic ras and either a control shRNA or an shRNA against ERK2. Cells with oncogenic ras and shRNA control entered senescence while cells with oncogenic ras and shRNA ERK2 bypassed senescence and underwent malignant transformation. Triplicates of these populations were used to purify total RNA, which we sent to Genome Quebec service for hybridization with Affymetrix microarrays.

2014-10-01 | E-GEOD-33613 | biostudies-arrayexpress

Expression data from human primary fibroblasts (IMR90) stably expressing H-RasV12 and shRNA against ERK2 or a non-targeting shRNA

2014-10-01 | GSE33613 | GEO

Distinct perturbation of the translatome by the anti-diabetic drug metformin

Project description:Reduced cancer incidence has been reported among type II diabetics treated with metformin. Metformin exhibits anti-proliferative and anti-neoplastic effects associated with inhibition of mTORC1, but the mechanisms are poorly understood. We provide the first genome-wide analysis of translational targets of canonical mTOR inhibitors (rapamycin and PP242) and metformin, revealing that metformin controls gene expression at the level of mRNA translation to an extent comparable to that of canonical mTOR inhibitors. Importantly, metformin's anti-proliferative activity can be explained by selective translational suppression of mRNAs encoding cell cycle regulators via the mTORC1/4E-BP pathway. Thus, metformin selectively inhibits mRNA translation of encoded proteins that promote neoplastic proliferation, motivating further studies of this compound and related biguanides in cancer prevention and treatment. MCF7 cells were treated with rapamycin, metformin or PP242 at concentrations that inhibited proliferation to 50% of control. Both cytoplasmic and polysome-associated mRNA was extracted from treatments and a vehicle treated control and probed with microarrays.

2012-05-20 | E-GEOD-36847 | biostudies-arrayexpress

Evaluation of microRNA expression in vehicle and metformin-treated breast cancer cells and evaluation of the dicer relevance

Project description:We have evaluated the microRNA expression profile of SUM159 cells stably infected with a control shRNA or a dicer-targeting shRNA treated with vehicle or metformin for 24 hrs at non cytotoxic doses. microRNA expression was evaluated from total RNA extracted from logaritmically growing SUM159 cells stably expressing a control shRNA or a dicer-targeting shRNA and treated with vehicle (PBS) or metformin (0.5mM) for 24 hrs.

2012-06-04 | E-GEOD-37038 | biostudies-arrayexpress

Distinct perturbation of the translatome by the anti-diabetic drug metformin

2012-05-21 | GSE36847 | GEO

Metformin Induces Dicer via Regulation of the RNA-binding protein AUF1

Project description:Metformin has been commonly used for decades to treat type 2 diabetes. Recent data indicates that mice treated with metformin live longer and healthier lives. Here, we show that chronic metformin exposure in mice and diabetics taking metformin have higher levels of the microRNA processing protein, Dicer. Examination of how metformin affects Dicer expression revealed that metformin alters binding of the AUF1 RNA-binding protein to DICER1 mRNA, which leads to stabilization of DICER1 mRNA. We found differential changes in microRNA expression in mice treated with metformin or caloric restriction, a proven life extending intervention. Several of these microRNAs are important for regulating cellular senescence and lifespan in model organisms. Consistent with this observation, treatment with metformin decreased cellular senescence in a Dicer-dependent manner. These data lead us to hypothesize that changes in Dicer levels may be important for organismal aging and that interventions that upregulate Dicer expression (e.g., metformin) may offer new therapeutic approaches to combat or prevent age-related diseases. Key words: diabetes mellitus, metformin, senescence, miRNA, RNA-binding proteins

2017-02-14 | GSE73393 | GEO

Expression data from kidney tissues treated with vehicle, losartan and metformin

Project description:Chronic kidney disease (CKD) is one of the major global health problems with high incidence, poor prognosis and high medical cost. However, few pharmacological options are available for CKD. Metformin is widely used for treatment of type-2 diabetes, but recent works showed that metformin ameliorates tumor progression, inflammatory disease and tissue fibrosis. Whether metformin ameliorates non-diabetic chronic glomerular disease and CKD is unexplored. Here we showed that metformin or losartan (used as control) has protective effects against CKD by suppressing proteinuria, renal inflammation, fibrosis and glomerular injury in Alport syndrome mouse model, which spontaneously manifests chronic glomerular and kidney disease. Transcriptome analysis showed that metformin and losartan influenced molecular pathways of metabolism and inflammation, respectively. While metformin specifically affected genes that were classified as metabolic regulators, losartan specifically altered genes that were classified as inflammatory regulators. Metformin also induced multiple signaling pathways not affected by losartan. Overall, metformin ameliorates non-diabetic chronic glomerular diseases, and could be considered a therapeutic option for CKD. We used microarrays to investigate the global gene expression underlying the protective effects of metformin on Alport syndrome mice model

2021-01-30 | GSE109861 | GEO

The NAMPT inhibitor FK866 increases metformin sensitivity in pancreatic cancer cells

Project description:Pancreatic cancer (pancreatic ductal adenocarcinoma: PDAC) is one of the most aggressive neoplastic diseases. Metformin use was associated with reduced pancreatic cancer incidence or better survival in diabetics. Metformin has been shown to inhibit PDAC cells survival and growth in vitro and in vivo. However, clinical trials using metformin failed to decrease pancreatic cancer progression in patients, raising important questions about molecular mechanisms that protect tumor cells from the antineoplastic activities of metformin. We confirm that metformin acts through inhibition of mitochondrial complex I, decreasing the NAD+/NADH ratio and that NAD+/NADH homeostasis determines metformin sensitivity in several cancer cell lines. Metabolites that can restore the NAD+/NADH ratio turned PDAC cells resistant to metformin. In addition, metformin treatment of PDAC cell lines induced a compensatory NAMPT expression increasing the pool of cellular NAD+. The NAMPT inhibitor FK866 sensitized PDAC cells to the antiproliferative effects of metformin in vitro and decreased cellular NAD+ pool. Intriguingly, FK866 combined with metformin increased survival in mice bearing KP4 cells xenografts but not in mice with PANC1 xenografts. Transcriptome analysis revealed that the drug combination reactivated genes in the p53 pathway and oxidative stress providing new insights about the mechanisms leading to cancer cell death.

2023-06-01 | GSE210562 | GEO

RNAseq of C. elegans cultured on metformin sensitive and resistant E. coli strains with and without 50mM metformin treatment.

Project description:Metformin is the therapy of choice for treating type 2 diabetes and is currently repurposed for a wide range of diseases including aging. Recent evidence implicates the gut microbiota as a site of metformin action. Combining two tractable genetic models, the bacterium E. coli and the nematode C. elegans, we performed C. elegans RNAseq to investigate the role of the metformin sensitive OP50 and metformin resistant OP50-MR E. coli microbiota in the drug effects on the host. Our data suggest an evolutionarily conserved bacterial mediation of metformin effects on host lipid metabolism and lifespan.

2019-07-13 | E-MTAB-7272 | biostudies-arrayexpress

Genome-wide CRISPR screen identifies synthetic lethality between DOCK1 inhibition and metformin in liver cancer

Project description:To explore how DOCK1 deficiency enhances the anti-tumor effects of metformin, we performed RNA-seq analysis in PLC cells expressing NTC or shDOCK1 in the presence or absence of metformin.

2021-12-31 | GSE181521 | GEO

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