RESUMEN
Transcriptional activation of target genes is essential for TP53-mediated tumour suppression, though the roles of the diverse TP53-activated target genes in tumour suppression remains poorly understood. Knockdown of ZMAT3, an RNA-binding zinc-finger protein involved in regulating alternative splicing, in haematopoietic cells by shRNA caused leukaemia only with the concomitant absence of the PUMA and p21, the critical effectors of TRP53-mediated apoptosis and cell cycle arrest respectively. We were interested to further investigate the role of ZMAT3 in tumour suppression beyond the haematopoietic system. Therefore, we generated Zmat3 knockout and compound gene knockout mice, lacking Zmat3 and p21, Zmat3 and Puma or all three genes. Puma-/-p21-/-Zmat3-/- triple knockout mice developed tumours at a significantly higher frequency compared to wild-type, Puma-/-Zmat3-/- or p21-/-Zmat3-/-deficient mice. Interestingly, we observed that the triple knockout and Puma-/-Zmat3-/- double deficient animals succumbed to lymphoma, while p21-/-Zmat3-/- animals developed mainly solid cancers. This analysis suggests that in addition to ZMAT3 loss, additional TRP53-regulated processes must be disabled simultaneously for TRP53-mediated tumour suppression to fail. Our findings reveal that the absence of different TRP53 regulated tumour suppressive processes changes the tumour spectrum, indicating that different TRP53 tumour suppressive pathways are more critical in different tissues.
Asunto(s)
Neoplasias , Proteína p53 Supresora de Tumor , Animales , Ratones , Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Incidencia , Ratones Noqueados , Neoplasias/genética , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismoRESUMEN
Colorectal cancer (CRC) is the second leading cause of cancer deaths. Though chemotherapy is the main treatment option for advanced CRC, patients invariably acquire resistance to chemotherapeutic drugs and fail to respond to the therapy. Although understanding the mechanisms regulating chemoresistance has been a focus of intense research to manage this challenge, the pathways governing resistance to drugs are poorly understood. In this study, we provide evidence for the role of ubiquitin ligase NEDD4 in resistance developed against the most commonly used CRC chemotherapeutic drug 5-fluorouracil (5-FU). A marked reduction in NEDD4 protein abundance was observed in a panel of CRC cell lines and patient-derived xenograft samples that were resistant to 5-FU. Knockout of NEDD4 in CRC cells protected them from 5-FU-mediated apoptosis but not oxaliplatin or irinotecan. Furthermore, NEDD4 depletion in CRC cells reduced proliferation, colony-forming abilities and tumour growth in mice. Follow-up biochemical analysis highlighted the inhibition of the JNK signalling pathway in NEDD4-deficient cells. Treatment with the JNK activator hesperidin in NEDD4 knockout cells sensitised the CRC cells against 5-FU. Overall, we show that NEDD4 regulates cell proliferation, colony formation, tumour growth and 5-FU chemoresistance in CRC cells.
Asunto(s)
Neoplasias Colorrectales , Fluorouracilo , Humanos , Animales , Ratones , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Línea Celular Tumoral , Resistencia a Antineoplásicos , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/uso terapéutico , Ratones Noqueados , Proliferación Celular , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismoRESUMEN
Extracellular vesicles (EVs) are small packages that are released by almost all types of cells. While the role of EVs in pathogenesis of certain diseases such as cancer is well established, EVs role in ocular health and disease is still at early stages of investigation. Given the significant role of EVs in pathological development and progression of diseases such as cancer, EVs present a similar opportunity for investigation in ocular pathophysiology. Studies have shown the presence of EVs in fluids from the ocular environment have close links with ocular health and disease. Hence, the cargo carried in EVs from ocular fluids can be used for monitoring disease phenotypes or therapeutic outcomes in eye-related disorders. Furthermore, in recent times EVs have increasingly gained attention as therapeutics and drug-delivery vehicles for treatment of eye diseases. There is a close relationship between EVs and mitochondria functioning with mitochondria dysfunction leading to a significant number of ophthalmic disorders. This review discusses the current knowledge of EVs in visual systems with a special focus on eye diseases resulting from dysfunctional mitochondria.
Asunto(s)
Vesículas Extracelulares , Oftalmopatías , Enfermedades Mitocondriales , Neoplasias , Humanos , Vesículas Extracelulares/metabolismo , Sistemas de Liberación de Medicamentos , Neoplasias/metabolismo , Oftalmopatías/metabolismo , MitocondriasRESUMEN
Inflammation is a natural defence mechanism of the body to protect against pathogens. It is induced by immune cells, such as macrophages and neutrophils, which are rapidly recruited to the site of infection, mediating host defence. The processes for eliminating inflammatory cells after pathogen clearance are critical in preventing sustained inflammation, which can instigate diverse pathologies. During chronic inflammation, the excessive and uncontrollable activity of the immune system can cause extensive tissue damage. New therapies aimed at preventing this over-activity of the immune system could have major clinical benefits. Here, we investigated the role of the pro-survival Bcl-2 family member A1 in the survival of inflammatory cells under normal and inflammatory conditions using murine models of lung and peritoneal inflammation. Despite the robust upregulation of A1 protein levels in wild-type cells upon induction of inflammation, the survival of inflammatory cells was not impacted in A1-deficient mice compared to wild-type controls. These findings indicate that A1 does not play a major role in immune cell homoeostasis during inflammation and therefore does not constitute an attractive therapeutic target for such morbidities.
Asunto(s)
Peritonitis , Neumonía , Animales , Apoptosis/fisiología , Supervivencia Celular , Inflamación/patología , RatonesRESUMEN
Extracellular vesicles (EVs) have been identified as novel mediators of intercellular communication. They work via delivering the sequestered cargo to cells in the close vicinity, as well as distant sites in the body, regulating pathophysiological processes. Cell death and inflammation are biologically crucial processes in both normal physiology and pathology. These processes are indistinguishably linked with their effectors modulating the other process. For instance, during an unresolvable infection, the upregulation of specific immune mediators leads to inflammation causing cell death and tissue damage. EVs have gained considerable interest as mediators of both cell death and inflammation during conditions, such as sepsis. This review summarizes the types of extracellular vesicles known to date and their roles in mediating immune responses leading to cell death and inflammation with specific focus on sepsis and lung inflammation.
Asunto(s)
Apoptosis , COVID-19/terapia , Muerte Celular , Vesículas Extracelulares/metabolismo , Inflamación/metabolismo , Pulmón/patología , SARS-CoV-2 , Sepsis/inmunología , Animales , Biomarcadores/metabolismo , COVID-19/inmunología , Comunicación Celular , Quimiocinas , Exosomas , Humanos , Pulmón/inmunología , Ratones , Sepsis/fisiopatologíaRESUMEN
The concept that extracellular vesicles (EVs) from the diet can be absorbed by the intestinal tract of the consuming organism, be bioavailable in various organs, and in-turn exert phenotypic changes is highly debatable. Here, we isolate EVs from both raw and commercial bovine milk and characterize them by electron microscopy, nanoparticle tracking analysis, western blotting, quantitative proteomics and small RNA sequencing analysis. Orally administered bovine milk-derived EVs survive the harsh degrading conditions of the gut, in mice, and is subsequently detected in multiple organs. Milk-derived EVs orally administered to mice implanted with colorectal and breast cancer cells reduce the primary tumor burden. Intriguingly, despite the reduction in primary tumor growth, milk-derived EVs accelerate metastasis in breast and pancreatic cancer mouse models. Proteomic and biochemical analysis reveal the induction of senescence and epithelial-to-mesenchymal transition in cancer cells upon treatment with milk-derived EVs. Timing of EV administration is critical as oral administration after resection of the primary tumor reverses the pro-metastatic effects of milk-derived EVs in breast cancer models. Taken together, our study provides context-based and opposing roles of milk-derived EVs as metastasis inducers and suppressors.
Asunto(s)
Vesículas Extracelulares , Leche/citología , Neoplasias Experimentales/patología , Administración Oral , Animales , Disponibilidad Biológica , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Bovinos , Línea Celular Tumoral , Proliferación Celular , Transición Epitelial-Mesenquimal , Vesículas Extracelulares/química , Vesículas Extracelulares/genética , Femenino , Humanos , Neoplasias Hepáticas Experimentales/patología , Neoplasias Hepáticas Experimentales/secundario , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Ratones Endogámicos BALB C , Neoplasias Experimentales/terapia , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Distribución Tisular , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Devil facial tumor disease (DFTD) and its lack of available therapies are propelling the Tasmanian devil population toward extinction. This study demonstrates that cholesterol homeostasis and carbohydrate energy metabolism sustain the proliferation of DFTD cells in a cell-type-dependent manner. In addition, we show that the liver-X nuclear receptor-ß (LXRß), a major cholesterol cellular sensor, and its natural ligand 24S-hydroxycholesterol promote the proliferation of DFTD cells via a metabolic switch toward aerobic glycolysis. As a proof of concept of the role of cholesterol homeostasis on DFTD proliferation, we show that atorvastatin, an FDA-approved statin-drug subtype used against human cardiovascular diseases that inhibits cholesterol synthesis, shuts down DFTD energy metabolism and prevents tumor growth in an in vivo DFTD-xenograft model. In conclusion, we show that intervention against cholesterol homeostasis and carbohydrate-dependent energy metabolism by atorvastatin constitutes a feasible biochemical treatment against DFTD, which may assist in the conservation of the Tasmanian devil.
Asunto(s)
Colesterol/metabolismo , Neoplasias Faciales/metabolismo , Neoplasias Faciales/veterinaria , Homeostasis , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Receptores X del Hígado/metabolismo , Marsupiales/metabolismo , Aerobiosis/efectos de los fármacos , Animales , Atorvastatina/farmacología , Proliferación Celular/efectos de los fármacos , Neoplasias Faciales/patología , Femenino , Glucólisis/efectos de los fármacos , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Oxiesteroles/farmacología , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoAsunto(s)
Anticuerpos Monoclonales/análisis , Antígenos de Histocompatibilidad Menor/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Animales , Anticuerpos Monoclonales/metabolismo , Células Cultivadas , Células HEK293 , Humanos , Ratones , Ratones Noqueados , Antígenos de Histocompatibilidad Menor/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Apoptosis-regulating BCL-2 family members, which can promote malignant transformation and resistance to therapy, have become prime therapeutic targets, as illustrated by the striking efficacy in certain lymphoid malignancies of the BCL-2-specific inhibitor venetoclax. In other lymphoid malignancies, however, such as the aggressive mantle cell lymphoma (MCL), cell survival might rely instead or also on BCL-2 relative MCL-1. We have explored MCL-1 as a target for killing MCL cells by both genetic and pharmacologic approaches. In several MCL cell lines, MCL-1 knockout with an inducible CRISPR/Cas9 system triggered spontaneous apoptosis. Accordingly, most MCL cell lines proved sensitive to the specific MCL-1 inhibitor S63845, and MCL-1 inhibition also proved efficacious in an MCL xenograft model. Furthermore, its killing efficacy rose on combination with venetoclax, the BCL-XL-specific inhibitor A-1331852, or Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, which reduced pro-survival signals. We also tested the MCL-1 inhibitor in primary samples from 13 MCL patients, using CD40L-expressing feeder cells to model their microenvironmental support. Notably, all unstimulated primary MCL samples were very sensitive to S63845, but the CD40L stimulation attenuated their sensitivity. Mass cytometric analysis revealed that the stimulation likely conveyed protection by elevating BCL-XL and MCL-1. Accordingly, sensitivity of the CD40L-stimulated cells to S63845 was substantially restored by co-treatment with venetoclax, the BCL-XL-specific inhibitor or ibrutinib. Overall, our findings indicate that MCL-1 is very important for survival of MCL cells and that the MCL-1 inhibitor, both alone and together with ibrutinib, venetoclax or a BCL-XL inhibitor, offers promise for novel improved MCL therapies.
Asunto(s)
Linfoma de Células del Manto/tratamiento farmacológico , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/antagonistas & inhibidores , Pirimidinas/farmacología , Tiofenos/farmacología , Proteína bcl-X/antagonistas & inhibidores , Animales , Antineoplásicos/farmacología , Apoptosis , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Proliferación Celular , Humanos , Linfoma de Células del Manto/metabolismo , Linfoma de Células del Manto/patología , Ratones , Ratones Endogámicos NOD , Ratones SCID , Sulfonamidas/farmacología , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Mutations in ß-catenin, especially at the residues critical for its degradation, render it constitutively active. Here, we show that mutant ß-catenin can be transported via extracellular vesicles (EVs) and activate Wnt signalling pathway in the recipient cells. An integrative proteogenomic analysis identified the presence of mutated ß-catenin in EVs secreted by colorectal cancer (CRC) cells. Follow-up experiments established that EVs released from LIM1215 CRC cells stimulated Wnt signalling pathway in the recipient cells with wild-type ß-catenin. SILAC-based quantitative proteomics analysis confirmed the transfer of mutant ß-catenin to the nucleus of the recipient cells. In vivo tracking of DiR-labelled EVs in mouse implanted with RKO CRC cells revealed its bio-distribution, confirmed the activation of Wnt signalling pathway in tumour cells and increased the tumour burden. Overall, for the first time, this study reveals that EVs can transfer mutant ß-catenin to the recipient cells and promote cancer progression.
RESUMEN
Extracellular vesicles (EVs) are membranous vesicles that are released by cells. In this study, the role of the Endosomal Sorting Complex Required for Transport (ESCRT) machinery in the biogenesis of yeast EVs was examined. Knockout of components of the ESCRT machinery altered the morphology and size of EVs as well as decreased the abundance of EVs. In contrast, strains with deletions in cell wall biosynthesis genes, produced more EVs than wildtype. Proteomic analysis highlighted the depletion of ESCRT components and enrichment of cell wall remodelling enzymes, glucan synthase subunit Fks1 and chitin synthase Chs3, in yeast EVs. Interestingly, EVs containing Fks1 and Chs3 rescued the yeast cells from antifungal molecules. However, EVs from fks1∆ or chs3∆ or the vps23∆chs3∆ double knockout strain were unable to rescue the yeast cells as compared to vps23∆ EVs. Overall, we have identified a potential role for yeast EVs in cell wall remodelling.
Asunto(s)
Pared Celular/metabolismo , Vesículas Extracelulares/metabolismo , Saccharomyces cerevisiae/citología , Saccharomyces cerevisiae/metabolismo , Antifúngicos/farmacología , Caspofungina/farmacología , Supervivencia Celular/efectos de los fármacos , Pared Celular/efectos de los fármacos , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Vesículas Extracelulares/efectos de los fármacos , Mutación/genética , Proteómica , Saccharomyces cerevisiae/efectos de los fármacos , Estrés Fisiológico/efectos de los fármacosRESUMEN
BCL-2 family proteins regulate the mitochondrial apoptotic pathway. BOK, a multidomain BCL-2 family protein, is generally believed to be an adaptor protein similar to BAK and BAX, regulating the mitochondrial permeability transition during apoptosis. Here we report that BOK is a positive regulator of a key enzyme involved in uridine biosynthesis; namely, uridine monophosphate synthetase (UMPS). Our data suggest that BOK expression enhances UMPS activity, cell proliferation, and chemosensitivity. Genetic deletion of Bok results in chemoresistance to 5-fluorouracil (5-FU) in different cell lines and in mice. Conversely, cancer cells and primary tissues that acquire resistance to 5-FU down-regulate BOK expression. Furthermore, we also provide evidence for a role for BOK in nucleotide metabolism and cell cycle regulation. Our results have implications in developing BOK as a biomarker for 5-FU resistance and have the potential for the development of BOK-mimetics for sensitizing 5-FU-resistant cancers.
Asunto(s)
Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Uridina/metabolismo , Animales , Apoptosis/efectos de los fármacos , Biomarcadores de Tumor/metabolismo , Proliferación Celular/efectos de los fármacos , Daño del ADN , Resistencia a Antineoplásicos/efectos de los fármacos , Fluorouracilo/farmacología , Mamíferos , Ratones , Complejos Multienzimáticos/metabolismo , Orotato Fosforribosiltransferasa/metabolismo , Orotidina-5'-Fosfato Descarboxilasa/metabolismo , Unión Proteica/efectos de los fármacos , Dominios Proteicos , Proteínas Proto-Oncogénicas c-bcl-2/química , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
IL-17-producing γδ T cells express oligoclonal Vγ4+ and Vγ6+ TCRs, mainly develop in the prenatal thymus, and later persist as long-lived self-renewing cells in all kinds of tissues. However, their exchange between tissues and the mechanisms of their tissue-specific adaptation remain poorly understood. Here, single-cell RNA-seq profiling identifies IL-17-producing Vγ6+ T cells as a highly homogeneous Scart1+ population in contrast to their Scart2+ IL-17-producing Vγ4+ T cell counterparts. Parabiosis demonstrates that Vγ6+ T cells are fairly tissue resident in the thymus, peripheral lymph nodes, and skin. There, Scart1+ Vγ6+ T cells display tissue-specific gene expression signatures in the skin, characterized by steady-state production of the cytokines IL-17A and amphiregulin as well as by high expression of the anti-apoptotic Bcl2a1 protein family. Together, this study demonstrates how Scart1+ Vγ6+ T cells undergo tissue-specific functional adaptation to persist as effector cells in their skin habitat.
Asunto(s)
Antígenos de Histocompatibilidad Menor/fisiología , Proteínas Proto-Oncogénicas c-bcl-2/fisiología , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Receptores de Superficie Celular/metabolismo , Análisis de la Célula Individual/métodos , Piel/inmunología , Subgrupos de Linfocitos T/inmunología , Transcriptoma , Animales , Supervivencia Celular , Células Cultivadas , Interleucina-17/genética , Interleucina-17/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores de Superficie Celular/genética , Piel/metabolismo , Piel/patologíaRESUMEN
Cancer cells actively release extracellular vesicles, including exosomes, into the surrounding microenvironment. Exosomes play pleiotropic roles in cancer progression and metastasis, including invasion, angiogenesis, and immune modulation. However, the proteome profile of exosomes isolated from cells with different metastatic potential and the role of these exosomes in driving metastasis remains unclear. Here, we conduct a comparative proteomic analysis of exosomes isolated from several genetically related mouse breast tumor lines with different metastatic propensity. The amount of exosomes produced and the extent of cancer-associated protein cargo vary significantly between nonmetastatic and metastatic cell-derived exosomes. Metastatic cell-derived exosomes contain proteins that promote migration, proliferation, invasion, and angiogenesis while the nonmetastatic cell-derived exosomes contain proteins involved in cell-cell/cell-matrix adhesion and polarity maintenance. The metastatic exosomes contain a distinct set of membrane proteins including Ceruloplasmin and Metadherin which could presumably aid in targeting the primary cancer cells to specific metastatic sites. Hence, it can be concluded that the exosomes contain different protein cargo based on the host cells metastatic properties and can facilitate in the dissemination of the primary tumors to distant sites.
Asunto(s)
Exosomas/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Mamarias Animales/metabolismo , Proteoma/metabolismo , Proteómica/métodos , Animales , Neoplasias Óseas/secundario , Adhesión Celular , Linaje de la Célula , Movimiento Celular , Proliferación Celular , Ceruloplasmina/metabolismo , Progresión de la Enfermedad , Femenino , Neoplasias Pulmonares/secundario , Neoplasias Mamarias Animales/patología , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos BALB C , Proteínas de Unión al ARN , Células Tumorales CultivadasRESUMEN
Extracellular vesicles (EVs) are a class of membranous vesicles that are released by multiple cell types into the extracellular environment. This unique class of extracellular organelles which play pivotal role in intercellular communication are conserved across prokaryotes and eukaryotes. Depending upon the cell origin and the functional state, the molecular cargo including proteins, lipids, and RNA within the EVs are modulated. Owing to this, EVs are considered as a subrepertoire of the host cell and are rich reservoirs of disease biomarkers. In addition, the availability of EVs in multiple bodily fluids including blood has created significant interest in biomarker and signaling research. With the advancement in high-throughput techniques, multiple EV studies have embarked on profiling the molecular cargo. To benefit the scientific community, existing free Web-based resources including ExoCarta, EVpedia, and Vesiclepedia catalog multiple datasets. These resources aid in elucidating molecular mechanism and pathophysiology underlying different disease conditions from which EVs are isolated. Here, the existing bioinformatics tools to perform integrated analysis to identify key functional components in the EV datasets are discussed.
Asunto(s)
Biología Computacional/métodos , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Investigación , Animales , Micropartículas Derivadas de Células , Bases de Datos Factuales , Exosomas , Humanos , Programas Informáticos , Navegador WebRESUMEN
The role of cortactin, a regulator of late endosomal trafficking, in the biogenesis and secretion of exosomes is poorly understood. In this issue, Sinha et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201601025) elucidate the role of cortactin as a positive regulator of late endosomal docking and exosome secretion.
Asunto(s)
Cortactina/metabolismo , Exosomas/metabolismo , Complejo 2-3 Proteico Relacionado con la Actina/metabolismo , Transporte Biológico , Línea Celular Tumoral , HumanosRESUMEN
BACKGROUND: To address the lack of standard terminology to describe extracellular RNA (exRNA) data/metadata, we have launched an inter-community effort to extend the Gene Ontology (GO) with subcellular structure concepts relevant to the exRNA domain. By extending GO in this manner, the exRNA data/metadata will be more easily annotated and queried because it will be based on a shared set of terms and relationships relevant to extracellular research. METHODS: By following a consensus-building process, we have worked with several academic societies/consortia, including ERCC, ISEV, and ASEMV, to identify and approve a set of exRNA and extracellular vesicle-related terms and relationships that have been incorporated into GO. In addition, we have initiated an ongoing process of extractions of gene product annotations associated with these terms from Vesiclepedia and ExoCarta, conversion of the extracted annotations to Gene Association File (GAF) format for batch submission to GO, and curation of the submitted annotations by the GO Consortium. As a use case, we have incorporated some of the GO terms into annotations of samples from the exRNA Atlas and implemented a faceted search interface based on such annotations. RESULTS: We have added 7 new terms and modified 9 existing terms (along with their synonyms and relationships) to GO. Additionally, 18,695 unique coding gene products (mRNAs and proteins) and 963 unique non-coding gene products (ncRNAs) which are associated with the terms: "extracellular vesicle", "extracellular exosome", "apoptotic body", and "microvesicle" were extracted from ExoCarta and Vesiclepedia. These annotations are currently being processed for submission to GO. CONCLUSIONS: As an inter-community effort, we have made a substantial update to GO in the exRNA context. We have also demonstrated the utility of some of the new GO terms for sample annotation and metadata search.
Asunto(s)
Vesículas Extracelulares/genética , Ontología de Genes , ARN/genética , Bases de Datos Genéticas , Humanos , Anotación de Secuencia Molecular , Navegador WebRESUMEN
Exosomes are membranous vesicles that are released by a variety of cells into the extracellular microenvironment and are implicated in intercellular communication. As exosomes contain RNA, proteins and lipids, there is a significant interest in characterizing the molecular cargo of exosomes. Here, we describe ExoCarta (http://www.exocarta.org), a manually curated Web-based compendium of exosomal proteins, RNAs and lipids. Since its inception, the database has been highly accessed (>54,000 visitors from 135 countries). The current version of ExoCarta hosts 41,860 proteins, >7540 RNA and 1116 lipid molecules from more than 286 exosomal studies annotated with International Society for Extracellular Vesicles minimal experimental requirements for definition of extracellular vesicles. Besides, ExoCarta features dynamic protein-protein interaction networks and biological pathways of exosomal proteins. Users can download most often identified exosomal proteins based on the number of studies. The downloaded files can further be imported directly into FunRich (http://www.funrich.org) tool for additional functional enrichment and interaction network analysis.