Exploration of the mechanisms underlying TNF-alpha resistance in breast cancer cells by a transcriptomic approach using an autophagy-dedicated microarray
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Muller Arnaud
PROVIDER: S-ECPF-MEXP-3074 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description:We used the autophagy microarray to profile the transcriptome of well-characterized TNF sensitive MCF-7 cell line and corresponding TNF-resistant 1001 clone.
2011-02-28 | E-MEXP-3074 | biostudies-arrayexpress
Project description:The rapid evolution of toxin resistance in animals has important consequences for the ecology of species and our economy. Pesticide resistance in insects has been a subject of intensive study; however, very little is known about how Drosophila species became resistant to natural toxins with ecological relevance, such as α-amanitin that is produced in deadly poisonous mushrooms. Here we performed a microarray study to elucidate the genes, chromosomal loci, molecular functions, biological processes, and cellular components that contribute to the α-amanitin resistance phenotype in Drosophila melanogaster. We suggest that toxin entry blockage through the cuticle, phase I and II detoxification, sequestration in lipid particles, and proteolytic cleavage of α-amanitin contribute in concert to this quantitative trait. We speculate that the resistance to mushroom toxins in D. melanogaster and perhaps in mycophagous Drosophila species has evolved as cross-resistance to pesticides, other xenobiotic substances, or environmental stress factors.
| S-EPMC3973583 | biostudies-literature
Project description:Exogenous methyl jasmonate (MeJA) application has shown promising effects on plant defense under diverse abiotic stresses. However, the mechanisms underlying MeJA-induced stress resistance in bananas are unclear. Therefore, in this study, we treated banana plants with 100 μM MeJA before inducing osmotic stress using mannitol. Plant phenotype and antioxidant enzyme activity results demonstrated that MeJA improved osmotic stress resistance in banana plants. Thereafter, to explore the molecular mechanisms underlying MeJA-induced osmotic stress resistance in banana seedlings, we conducted high-throughput RNA sequencing (RNA-seq) using leaf and root samples of "Brazilian" banana seedlings treated with MeJA for 0 h and 8 h. RNA-seq analysis showed that MeJA treatment upregulated 1506 (leaf) and 3341 (root) genes and downregulated 1768 (leaf) and 4625 (root) genes. Then, we performed gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses on the differentially expressed genes. We noted that linoleic acid metabolism was enriched in both root and leaf samples, and the genes of this pathway exhibited different expression patterns; 9S-LOX genes were highly induced by MeJA in the leaves, whereas 13S-LOX genes were highly induced in the roots. We also identified the promoters of these genes, as the differences in response elements may contribute to tissue-specific gene expression in response to MeJA application in banana seedlings. Overall, the findings of this study provide insights into the mechanisms underlying abiotic stress resistance in banana that may aid in the improvement of banana varieties relying on molecular breeding.
| S-EPMC10935223 | biostudies-literature
Project description:Over the past decade, large-scale genetic studies have successfully identified hundreds of genetic variants robustly associated with risk for psychiatric disorders. However, mechanistic insight and clinical translation continue to lag the pace of risk variant identification, hindered by the sheer number of targets and their predominant noncoding localization, as well as pervasive pleiotropy and incomplete penetrance. Successful next steps require identification of "causal" genetic variants and their proximal biological consequences; placing variants within biologically defined functional contexts, reflecting specific molecular pathways, cell types, circuits, and developmental windows; and characterizing the downstream, convergent neurobiological impact of polygenicity within an individual. Here, we discuss opportunities and challenges of high-throughput transcriptomic profiling in the human brain, and how transcriptomic approaches can help pinpoint mechanisms underlying genetic risk for psychiatric disorders at a scale necessary to tackle daunting levels of polygenicity. These include transcriptome-wide association studies for risk gene prioritization through integration of genome-wide association studies with expression quantitative trait loci. We outline transcriptomic results that inform our understanding of the brain-level molecular pathology of psychiatric disorders, including autism spectrum disorder, bipolar disorder, major depressive disorder, and schizophrenia. Finally, we discuss systems-level approaches for integration of distinct genetic, genomic, and phenotypic levels, including combining spatially resolved gene expression and human neuroimaging maps. Results highlight the importance of understanding gene expression (dys)regulation across human brain development as a major contributor to psychiatric disease pathogenesis, from common variants acting as expression quantitative trait loci to rare variants enriched for gene expression regulatory pathways.
| S-EPMC7718368 | biostudies-literature
Project description:The rapid evolution of toxin resistance in animals has important consequences for the ecology of species and our economy. Pesticide resistance in insects has been a subject of intensive study, however, very little is known about how Drosophila species became resistant to natural toxins with ecological relevance, such as α-amanitin that is produced in deadly poisonous mushrooms. Here we performed a microarray study to elucidate the genes, chromosomal loci, molecular functions, biological processes, and cellular components that contribute to the α-amanitin resistance phenotype in Drosophila melanogaster. We suggest that toxin entry blockage through the cuticle, phase I and II detoxification, sequestration in lipid particles, and proteolytic cleavage of α-amanitin contribute in concert to this quantitative trait. We speculate that the resistance to mushroom toxins in Drosophila melanogaster and perhaps in mycophagous Drosophila species has evolved as a cross-resistance to pesticides or other xenobiotic substances.
2015-12-01 | GSE52782 | GEO
Project description:Selective autophagy specifically eliminates damaged or superfluous organelles, maintaining cellular health. In this process, a double membrane structure termed an autophagosome captures target organelles or proteins and delivers this cargo to the lysosome for degradation. The attachment of the small protein ubiquitin to cargo has emerged as a common mechanism for initiating organelle or protein capture by the autophagy machinery. In this process, a suite of ubiquitin-binding cargo receptors function to initiate autophagosome assembly in situ on the target cargo, thereby providing selectivity in cargo capture. Here, we review recent efforts to understand the biochemical mechanisms and principles by which cargo are marked with ubiquitin and how ubiquitin-binding cargo receptors use conserved structural modules to recruit the autophagosome initiation machinery, with a particular focus on mitochondria and intracellular bacteria as cargo. These emerging mechanisms provide answers to long-standing questions in the field concerning how selectivity in cargo degradation is achieved.
| S-EPMC9254164 | biostudies-literature
Project description:BackgroundMyxozoan parasites infect fish worldwide causing significant disease or death in many economically important fish species, including rainbow trout and steelhead trout (Oncorhynchus mykiss). The myxozoan Ceratonova shasta is a parasite of salmon and trout that causes ceratomyxosis, a disease characterized by severe inflammation in the intestine resulting in hemorrhaging and necrosis. Populations of O. mykiss that are genetically fixed for resistance or susceptibility to ceratomyxosis exist naturally, offering a tractable system for studying the immune response to myxozoans. The aim of this study was to understand how steelhead trout that are resistant to the disease respond to C. shasta once it has become established in the intestine and identify potential mechanisms of resistance.ResultsSequencing of intestinal mRNA from resistant steelhead trout with severe C. shasta infections identified 417 genes differentially expressed during the initial stage of the infection compared to uninfected control fish. A strong induction of interferon-gamma and interferon-stimulated genes was evident, along with genes involved in cell adhesion and migration. A total of 11,984 genes were differentially expressed during the late stage of the infection, most notably interferon-gamma, interleukin-6, and immunoglobulin transcripts. A distinct hardening of the intestinal tissue and a strong inflammatory reaction in the intestinal submucosa including severe hyperplasia and inflammatory cell infiltrates were observed in response to the infection. The massive upregulation of caspase-14 early in the infection, a protein involved in keratinocyte differentiation might reflect the rapid onset of epithelial repair mechanisms, and the collagenous stratum compactum seemed to limit the spread of C. shasta within the intestinal layers. These observations could explain the ability of resistant fish to eventually recover from the infection.ConclusionsOur results suggest that resistance to ceratomyxosis involves both a rapid induction of key immune factors and a tissue response that limits the spread of the parasite and the subsequent tissue damage. These results improve our understanding of the myxozoan-host dialogue and provide a framework for future studies investigating the infection dynamics of C. shasta and other myxozoans.
| S-EPMC8467531 | biostudies-literature
Project description:Potato virus Y (PVY) mainly infects Solanaceous crops, resulting in considerable losses in the yield and quality. Iron (Fe) is involved in various biological processes in plants, but its roles in resistance to PVY infection has not been reported. In this study, foliar application of Fe could effectively inhibit early infection of PVY, and a full-length transcriptome and Illumina RNA sequencing was performed to investigate its modes of action in PVY-infected Nicotiana tabacum. The results showed that 18,074 alternative splicing variants, 3,654 fusion transcripts, 3,086 long non-coding RNAs and 14,403 differentially expressed genes (DEGs) were identified. Specifically, Fe application down-regulated the expression levels of the DEGs related to phospholipid hydrolysis, phospholipid signal, cell wall biosynthesis, transcription factors (TFs) and photosystem I composition, while those involved with photosynthetic electron transport chain (PETC) were up-regulated at 1 day post inoculation (dpi). At 3 dpi, these DEGs related to photosystem II composition, PETC, molecular chaperones, protein degradation and some TFs were up-regulated, while those associated with light-harvesting, phospholipid hydrolysis, cell wall biosynthesis were down-regulated. At 9 dpi, Fe application had little effects on resistance to PVY infection and transcript profiles. Functional analysis of these potentially critical DEGs was thereafter performed using virus-induced gene silencing approaches and the results showed that NbCat-6A positively regulates PVY infection, while the reduced expressions of NbWRKY26, NbnsLTP, NbFAD3 and NbHSP90 significantly promote PVY infection in N. benthamiana. Our results elucidated the regulatory network of Fe-mediated resistance to PVY infection in plants, and the functional candidate genes also provide important theoretical bases to further improve host resistance against PVY infection.
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Project description:The lung is inhabited by resident alveolar and interstitial macrophages as well as monocytic cells that survey lung tissues. Each cell type plays distinct functional roles under homeostatic and inflammatory conditions, but mechanisms establishing their molecular identities and functional potential remain poorly understood. In the present study, systematic evaluation of transcriptomes and open chromatin of alveolar macrophages (AMs), interstitial macrophages (IMs) and lung monocytes from two mouse strains enabled inference of common and cell-specific transcriptional regulators. We provide evidence that these factors drive selection of regulatory landscapes that specify distinct phenotypes of AMs and IMs and entrain qualitatively different responses to toll-like receptor 4 signaling in vivo. These studies reveal a striking divergence in a fundamental innate immune response pathway in AMs and establish a framework for further understanding macrophage diversity in the lung.
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Project description:Colonization of human skin and nares by methicillin-resistant Staphylococcus aureus (MRSA) leads to community spread of MRSA. This spread is exacerbated by transfer of MRSA between humans and livestock, particularly swine. Here we capitalized on the shared features between human and porcine skin, including shared MRSA colonization, to study novel bacterial mediators of MRSA colonization resistance. We focused on the poorly studied bacterial species Desemzia incerta, which we found to exert antimicrobial activity through a secreted product and exhibited colonization resistance against MRSA in an in vivo murine skin model. Using parallel genomic and biochemical investigation, we discovered that D. incerta secretes an antimicrobial protein. Sequential protein purification and proteomics analysis identified 24 candidate inhibitory proteins, including a promising peptidoglycan hydrolase candidate. Aided by transcriptional analysis of D. incerta and MRSA cocultures, we found that exposure to D. incerta leads to decreased MRSA biofilm production. These results emphasize the value in exploring microbial communities across a spectrum of hosts, which can lead to novel therapeutic agents as well as increased understanding of microbial competition.
| S-EPMC10592716 | biostudies-literature