Microenvironment commits breast tumor ECs to dedifferentiation by micro-RNA-200-b-3p regulation and extracellular matrix remodelling (miRNA-Seq)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA929975 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23290070.fastq.gz | Fastqsanger.gz | |||
| SRR23290071.fastq.gz | Fastqsanger.gz | |||
| SRR23290072.fastq.gz | Fastqsanger.gz | |||
| SRR23290073.fastq.gz | Fastqsanger.gz |
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Project description:Hypoxia shapes the tumor microenvironment and modulates distinct cell populations activity. Low pO2 activates pathological angiogenesis in cancer- process in which endothelial cells (ECs) are the most important players. The main goal of the study was to evidence the hypoxic tumor microenvironment influence on the global gene expression pattern characteristic for ECs and evidence the distinct and specific responses displayed by the tumor-derived ECs compared to the healthy endothelium during the endothelial to mesenchymal transition (EndMT) and its regulation by miR-200-b-3p. Immortalized lines of ECs from the same patient with diagnosed breast cancer- healthy breast tissue (HBH.MEC) and primary tumor (HBCa.MEC) were used. The experiments were performed in normoxia and hypoxia for 48 hours. By wound healing test, we investigated the migration abilities of ECs. Using the established model, global gene expression analysis with NGS was carried out to detect new pathways altered in pathological ECs and to find the most changed miRNAs. The validation of NGS data from RNA and miRNA was estimated by qPCRs. Hypoxia influences ECs migration properties in wound healing assay. In hypoxia, healthy ECs migrate slower than in normoxia, as opposed to HBCa.MEC where no decreased migration ability was induced by hypoxia, due to EndMT features. NGS data identified this process to be altered in cancer ECs through extracellular matrix (ECM) organization. The deregulated genes, confirmed by qPCR, included: SPP1, ITGB6, COL4A4, ADAMST2, LAMA1, GAS6, AGTR2, PECAM1, ELN, FBLN2, COL6A3, COL9A3. NGS also identified collagens, laminin, fibronectin and integrin, as being deregulated in tumor-derived ECs. Moreover, the analysis of ten most intensively modified miRNAs when breast tumor-derived ECs were compared to healthy ECs, put a light on miR-200b-3p which is strongly up-regulated in HBCa.MECs as compared to HBH.MECs. Microenvironment influences on ECs dedifferentiation by miR-200-b-3p and ECM. The pathological ECs differed significantly, both phenotypically and functionally, from the normal corresponding tissue, thus influencing their microenvironment cross- talk. The gene expression profile confirms the EndMT phenotype of tumor-derived ECs and migratory properties acquisition. Moreover, it indicates the role of miR-200b-3p, regulating EndMT in pathological ECs, silencing several angiogenic growth factors and their receptors by directly targeting their mRNA transcripts.
2023-04-01 | GSE224147 | GEO
Project description:Introduction: Hypoxia shapes the tumor microenvironment, modulates distinct cell population activities, and activates pathological angiogenesis in cancer, where endothelial cells (ECs) are the most important players. This study aimed to evidence the influences of the tumor microenvironment on the global gene expression pattern characteristic for ECs and the distinct responses displayed by tumor-derived ECs in comparison to the healthy endothelium during endothelial to mesenchymal transition (EndMT) and its regulation by miR-200-b-3p. Methodology: Immortalized lines of ECs from the same patient with breast cancer, healthy breast tissue (HBH.MEC), and primary tumor (HBCa.MEC) were used. The experiments were performed in normoxia and hypoxia for 48 h. By using the wound healing test, we investigated the migration abilities of ECs. Global gene expression analysis with NGS was carried out to detect new pathways altered in pathological ECs and find the most changed miRNAs. The validation of NGS data from RNA and miRNA was estimated by qPCRs. Mimic miR-200b-3p was used in HBH.MEC, and the targets VEGF, Bcl2, ROCK2, and SP1 were checked. Results: Hypoxia influences EC migration properties in wound healing assays. In hypoxia, healthy ECs migrate slower than they do in normoxia, as opposed to HBCa.MEC, where no decreased migration ability is induced by hypoxia due to EndMT features. NGS data identified this process to be altered in cancer ECs through extracellular matrix (ECM) organization. The deregulated genes, validated by qPCR, included SPP1, ITGB6, COL4A4, ADAMST2, LAMA1, GAS6, PECAM1, ELN, FBLN2, COL6A3, and COL9A3. NGS also identified collagens, laminins, fibronectins, and integrins, as being deregulated in tumor-derived ECs. Moreover, the analysis of the 10 most intensively modified miRNAs, when breast tumor-derived ECs were compared to healthy ECs, shed light on miR-200b-3p, which is strongly upregulated in HBCa.MECs when compared to HBH.MECs. Discussion and conclusion: The pathological ECs differed significantly, both phenotypically and functionally, from the normal corresponding tissue, thus influencing their microenvironment cross-talk. The gene expression profile confirms the EndMT phenotype of tumor-derived ECs and migratory properties acquisition. Moreover, it indicates the role of miR-200b-3p, that is, regulating EndMT in pathological ECs and silencing several angiogenic growth factors and their receptors by directly targeting their mRNA transcripts.
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2011-01-01 | E-GEOD-22353 | biostudies-arrayexpress
Project description:Ecs is an ATP-binding cassette (ABC) transporter present in aerobic and facultative anaerobic gram-positive Firmicutes. Inactivation of Bacillus subtilis Ecs causes pleiotropic changes in the bacterial phenotype including inhibition of intramembrane proteolysis. The molecule(s) transported by Ecs is (are) still unknown. In this study we mutated the ecsAB operon in two Staphylococcus aureus strains, Newman and LS-1. Phenotypic and functional characterization of these Ecs deficient mutants revealed a defect in growth, increased autolysis and lysostaphin sensitivity, altered composition of cell wall proteins including the precursor form of staphylokinase and an altered bacterial surface texture. DNA microarray analysis indicated that the Ecs deficiency changed expression of the virulence factor regulator protein Rot accompanied by differential expression of membrane transport proteins, particularly ABC transporters and phosphate-specific transport systems, protein A, adhesins and capsular polysaccharide biosynthesis proteins. Virulence of the ecs mutants was studied in a mouse model of hematogenous S. aureus infection. Mice inoculated with the ecs mutant strains developed markedly milder infections than those inoculated with the wild-type strains and had consequently lower mortality, less weight loss, milder arthritis and decreased persistence of staphylococci in the kidneys. The ecs mutants had higher susceptibility to ribosomal antibiotics and plant alkaloids chelerythrine and sanguinarine. Our results show that Ecs is essential for staphylococcal virulence and antimicrobial resistance probably since the transport function of Ecs is essential for the normal structure and function of the cell wall. Thus targeting Ecs may be a new approach in combating staphylococcal infection.
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