RESUMO
Injection of OCs into adult male flies induces a strong transcriptomic response in the host flies featuring in particular genes encoding bona fide G coupled proteins, among which the gene for methuselah like 1 is prominent. The injection is followed after a 3-d lag period, by the proliferation of the oncogenic cells. We hypothesized that through the product of mthl1 the host might control, at least in part, this proliferation as a defense reaction. Through a combination of genetic manipulations of the mthl1 gene (loss of function and overexpression of mthl1), we document that indeed this gene has an antiproliferative effect. Parallel injections of primary embryonic Drosophila cells or of various microbes do not exhibit this effect. We further show that mthl1 controls the expression of a large number of genes coding for chemoreceptors and genes implicated in regulation of development. Of great potential interest is our observation that the expression of the mouse gene coding for the adhesion G-protein-coupled receptor E1 (Adgre1, also known as F4/80), a potential mammalian homologue of mthl1, is significantly induced by B16-F10 melanoma cell inoculation 3 d postinjection in both the bone marrow and spleen (nests of immature and mature myeloid-derived immune cells), respectively. This observation is compatible with a role of this GPCR in the early response to injected tumor cells in mice.
Assuntos
Proteínas de Drosophila , Drosophila , Animais , Masculino , Camundongos , Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Perfilação da Expressão Gênica , Mamíferos/genética , Células Mieloides/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismoRESUMO
We have injected dish-cultured oncogenic RasV12 cells into adult male flies and analyzed by single cell transcriptomics their destiny within the host after 11 days. We identified in the preinjection samples and in the 11-day postinjection samples in all 16 clusters of cells, of which 5 disappeared during the experiment in the host. The other cell clusters expanded and expressed genes involved in the regulation of cell cycle, metabolism, and development. In addition, three clusters expressed genes related to inflammation and defense. Predominant among these were genes coding for phagocytosis and/or characteristic for plasmatocytes (the fly equivalent of macrophages). A pilot experiment indicated that the injection into flies of oncogenic cells, in which two of most strongly expressed genes had been previously silenced by RNA interference, into flies resulted in a dramatic reduction of their proliferation in the host flies as compared to controls. As we have shown earlier, the proliferation of the injected oncogenic cells in the adult flies is a hallmark of the disease and induces a wave of transcriptions in the experimental flies. We hypothesize that this results from a bitter dialogue between the injected cells and the host, while the experiments presented here should contribute to deciphering this dialogue.
Assuntos
Drosophila melanogaster , Análise da Expressão Gênica de Célula Única , Células Tumorais Cultivadas , Masculino , Animais , Inflamação , Transdução de Sinais , Fagocitose , Peptídeos AntimicrobianosRESUMO
Enhancer RNAs (eRNAs), a subclass of noncoding RNAs from enhancers, have been demonstrated to exhibit important regulatory effects on the expressions of various genes. However, the role of eRNAs in skin cutaneous melanoma (SKCM) remained largely unclear. In this study, we aimed to explore the expression and prognostic value of an enhancer RNA TEX41 in SKCM as well as the associations between TEX41 and tumor-infiltrating immune cells (TICs). We observed that TEX41 expression was distinctly increased in SKCM specimens compared with normal skin specimens using GEPIA. Survival assays based on TGCA datasets revealed that patients with low TEX41 expressions displayed a longer overall survival than those with high TEX41 expression. CIBERSORT datasets revealed that TEX41 was related to 8 types of TICs (macrophages M1, T cells regulatory, plasma cells, mast cells resting, T cells CD8, dendritic cells resting, and T cells follicular helper). Three kinds of TICs were negatively related to TEX41 expressions, including macrophages M2, NK cells resting, and macrophages M0. The expressions of TEX41 were involved in five KEGG pathways, including transcriptional misregulation in cancer, SNARE interactions in vesicular transport, mitophagy-animal, melanoma, melanogenesis, and progesterone-mediated oocyte maturation. Overall, TEX41 can be used as a novel biomarker for the prognosis of SKCM patients and is associated with TICs, indicating it as a therapeutic target for SKCM.
Assuntos
Biomarcadores Tumorais/análise , Regulação Neoplásica da Expressão Gênica , Linfócitos do Interstício Tumoral/imunologia , Melanoma/imunologia , RNA Longo não Codificante/genética , Neoplasias Cutâneas/imunologia , Microambiente Tumoral , Linfócitos T CD8-Positivos/imunologia , Estudos de Casos e Controles , Humanos , Melanoma/genética , Melanoma/patologia , Prognóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Melanoma Maligno CutâneoRESUMO
We previously reported that an ortholog of STING regulates infection by picorna-like viruses in Drosophila In mammals, STING is activated by the cyclic dinucleotide 2'3'-cGAMP produced by cGAS, which acts as a receptor for cytosolic DNA. Here, we showed that injection of flies with 2'3'-cGAMP induced the expression of dSTING-regulated genes. Coinjection of 2'3'-cGAMP with a panel of RNA or DNA viruses resulted in substantially reduced viral replication. This 2'3'-cGAMP-mediated protection was still observed in flies with mutations in Atg7 and AGO2, genes that encode key components of the autophagy and small interfering RNA pathways, respectively. By contrast, this protection was abrogated in flies with mutations in the gene encoding the NF-κB transcription factor Relish. Transcriptomic analysis of 2'3'-cGAMP-injected flies revealed a complex response pattern in which genes were rapidly induced, induced after a delay, or induced in a sustained manner. Our results reveal that dSTING regulates an NF-κB-dependent antiviral program that predates the emergence of interferons in vertebrates.
Assuntos
Proteínas de Drosophila/metabolismo , Proteínas de Membrana/metabolismo , NF-kappa B/metabolismo , Nucleotídeos Cíclicos/metabolismo , Fatores de Transcrição/metabolismo , Vírus/metabolismo , Animais , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Proteína 7 Relacionada à Autofagia/genética , Proteína 7 Relacionada à Autofagia/metabolismo , Proteínas de Drosophila/genética , Drosophila melanogaster , Proteínas de Membrana/genética , Mutação , NF-kappa B/genética , Nucleotídeos Cíclicos/genética , Fatores de Transcrição/genética , Vírus/genéticaRESUMO
Pure SnO2 and Y-doped SnO2 nanobelts were prepared by thermal evaporation at 1350 °C in the presence of Ar carrier gas (30 sccm). The samples were characterized by scanning electron microscope (SEM), X-ray diffraction (XRD), energy dispersion spectrometer (EDS), X-ray photoelectron spectrometer (XPS), UV-Vis absorption spectroscopy, Raman spectroscopy, and Fourier transform infrared spectrum (FTIR). The sensing properties of the devices based on a single SnO2 nanobelt and Y-doped SnO2 nanobelt were explored to acetone, ethanol, and ethanediol. It reveals that the sensitivity of single Y-doped SnO2 nanobelt device is 11.4 to 100 ppm of acetone at 210 °C, which is the highest response among the three tested VOC gases. Y3+ ions improve the sensitivity of SnO2 sensor and have an influence on the optical properties of Y-doped SnO2 nanobelts.
