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Nutrient-restriction activated Fra-2 promotes tumor progression in Mir15aKO pancreatic cancer

ABSTRACT: Nutrient-restriction activated Fra-2 promotes tumor progression in Mir15aKO pancreatic cancer

PROVIDER: PRJNA994093 | ENA |

REPOSITORIES: ENA

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Nutrient-restriction activated Fra-2 promotes tumor progression in Mir15aKO pancreatic cancer

Project description:We used microarrays to identify genes dysregulated in cellular stress response to nutrient deprivation in an inducible mouse model of Mir15aKO PDAC Expression data of pancreatic cancer collected from genetic mouse model KrasLSL-G12D/Ptf1aCre-ERTM/Ptenflox (named KPP mouse) and KrasLSL-G12D/Ptf1aCre-ERTM/Ptenflox/Mir15aKO (named GL mouse) fed with Control diet (C-diet, 20% protein) and isocaloric, low-protein diet (LP-diet, 5% protein)

2023-07-17 | GSE237163 | GEO

Nutrient restriction-activated Fra-2 promotes tumor progression via IGF1R in miR-15a downmodulated pancreatic ductal adenocarcinoma.

Project description:Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, characterized by an intense desmoplastic reaction that compresses blood vessels and limits nutrient supplies. PDAC aggressiveness largely relies on its extraordinary capability to thrive and progress in a challenging tumor microenvironment. Dysregulation of the onco-suppressor miR-15a has been extensively documented in PDAC. Here, we identified the transcription factor Fos-related antigen-2 (Fra-2) as a miR-15a target mediating the adaptive mechanism of PDAC to nutrient deprivation. We report that the IGF1 signaling pathway was enhanced in nutrient deprived PDAC cells and that Fra-2 and IGF1R were significantly overexpressed in miR-15a downmodulated PDAC patients. Mechanistically, we discovered that miR-15a repressed IGF1R expression via Fra-2 targeting. In miR-15a-low context, IGF1R hyperactivated mTOR, modulated the autophagic flux and sustained PDAC growth in nutrient deprivation. In a genetic mouse model, Mir15aKO PDAC showed Fra-2 and Igf1r upregulation and mTOR activation in response to diet restriction. Consistently, nutrient restriction improved the efficacy of IGF1R inhibition in a Fra-2 dependent manner. Overall, our results point to a crucial role of Fra-2 in the cellular stress response due to nutrient restriction typical of pancreatic cancer and support IGF1R as a promising and vulnerable target in miR-15a downmodulated PDAC.

| S-EPMC10859382 | biostudies-literature

Transcription profiling of rat RK3E cells overexpressing activated TrkB following retroviral silencing of Fra-1

Project description:Silencing of Fra-1 in RK3E cells overexpressing activated TrkB

2009-04-29 | E-NCMF-20 | biostudies-arrayexpress

Expression data of A549 Fra-2 overexpressing cells

Project description:Fra-2 belongs to the activated protein-1 (AP-1) family and is involved in the mechanisms of resistance to platinum in ovarian cancer and to anti-EGFR therapy in NSCLC. We used microarrays to identify genes potentially regulated by Fra-2 transciptional activity.

2022-09-23 | GSE213816 | GEO

Comparative analysis of gene expression in Fra-1+/+ and Fra-1-/- mice lung

2014-05-22 | GSE43695 | GEO

Identification of Fra-1 and/or Fra-2 regulated genes in MDA-MB231 cells

Project description:In the paper "Fra-1 regulates its target genes via binding to remote enhancers without exerting major control on chromatin architecture in triple negative breast cancers" by Bejjani et al., we identified Fra-1 and/or Fra-2 target genes in MDA-MB-231 cells. si RNA against Fra-1 and against Fra-2 were transfected in MDA-MB-231 cells either independenlty or simultaneously to identify genes regulated specifically by Fra-1 or Fra-2 and genes regulated redundantly or complementarily by Fra-1 and Fra-2 total RNA were purified and biotinylated sense-strand cDNA were produced. cDNA targets were used to probe Affymetrix GeneChip Human Gene 2.0 ST arrays

2021-02-23 | GSE146823 | GEO

Comparative analysis of gene expression in Fra-1+/+ and Fra-1-/- mice lung

Project description:We hypothesized that gene expression in lungs of Fra-1+/+ and Fra-1-/- mice are divergent thus contributing fibrosis. More specifically, Fra-1-/- mice are increased susceptible to fibrosis. In order to test these hypotheses at the gene expression level, we utilized microarray analysis to examine transcriptional differences between Fra-1+/+ and Fra-1-/- mice at early time point. This study utilizes microarray analysis to test these hypotheses. 5 days PBS and bleomycin treated lung samples from both Fra-1+/+ and Fra-1-/- mice were used. RNA was isolated and used for global gene expression profiling (Affymetrix MoGene 1.0ST v1 Array). The raw probe signal intensities were quantile normalized over all samples, summarized with the robust multi-array average (RMA) algorithm and log2 transformed with a median polish, using the Affymetrix Power Tools. We considered a transcript cluster (gene-level) to be reliably expressed in a sample if the Affymetrix implemented DABG (detection above ground) p-value was less than 0.05. We used local-pooled-error (LPE) estimates and robust statistical tests for evaluating significance of each gene's differential expression in a comparison.

2014-05-22 | E-GEOD-43695 | biostudies-arrayexpress

Transcript profiling in peritoneal macrophages from wildtype, Fra-1ΔMxCre or Fra-2ΔLysMCre mice

Project description:The polarization and activation of macrophages are controlled synergistically by transcription factors such as NF-κB and AP-1 transcription factor members. Surprisingly, little is known about the role of the Fra proteins, both members of the AP-1 transcription factor family, in macrophage activity. To determine the full profile of Fra network, microarray RNA expression analysis using Agilent Technologies platform was performed in wild-type, Fra-1ΔMxCre or Fra-2ΔLysMCre macrophages.

2021-05-17 | GSE128787 | GEO

Placental transcriptome adaptations to maternal nutrient restriction in sheep

Project description:Placental transcriptome adaptations to maternal nutrient restriction in sheep

| PRJNA746985 | ENA

Mitochondrial homeostasis of endocrine organ navigates nutrient restriction checkpoint

Project description:Mitochondrial homeostasis of endocrine organ navigates nutrient restriction checkpoint

| PRJNA1110747 | ENA