-
1
المؤلفون: Yulya I. Savinovskaya, Anna A. Nushtaeva, Anna V. Savelyeva, Vitaliy V. Morozov, Elena I. Ryabchikova, Elena V. Kuligina, Vladimir A. Richter, Dmitriy V. Semenov
المصدر: Current Issues in Molecular Biology; Volume 44; Issue 12; Pages: 6028-6045
مصطلحات موضوعية: Microbiology (medical), General Medicine, human blood extracellular vesicles, transcriptome, extracellular RNA, next-generation sequencing, A549 cells, NF-кB signaling, Molecular Biology, Microbiology
الوصف: Extracellular vesicles (EVs) produced by various cell types are heterogeneous in size and composition. Changes in the RNA sets of EVs in biological fluids are considered the basis for the development of new approaches to minimally invasive diagnostics and the therapy of human diseases. In this study, EVs were obtained from the blood of healthy donors by centrifugation, followed by ultracentrifugation. It was shown that EVs consist of several populations including small exosome-like vesicles and larger microvesicle-like particles. The composition of EVs’ RNAs was determined. A549 lung adenocarcinoma cells were incubated with EV and the NGS analysis of differentially expressed genes was performed. During the incubation of A549 cells with EVs, the levels of mRNA encoding components for the NF-kB signaling pathway increased, as well as the expression of genes controlled by the NF-kB transcription factor. Overall, our results suggest that components of EVs trigger the NF-kB signaling cascade in A549 cells, leading to the transcription of genes including cytokines, adhesion molecules, cell cycle regulators, and cell survival factors. Our data provide insight into the interaction between blood EVs and human cells and can be used for designing new tools for the diagnosis and treatment of human diseases.
وصف الملف: application/pdf
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::050ed187857de81d56a365e55218412d
https://doi.org/10.3390/cimb44120411 -
2
المؤلفون: Soekmadji, Carolina, Hill, Andrew F, Wauben, Marca H, Buzás, Edit I, Di Vizio, Dolores, Gardiner, Chris, Lötvall, Jan, Sahoo, Susmita, Witwer, Kenneth W, dB&C I&I, LS Celbiologie-Algemeen
المساهمون: dB&C I&I, LS Celbiologie-Algemeen
المصدر: Journal of Extracellular Vesicles, Vol 7, Iss 1 (2018)
Journal of Extracellular Vesicles
Journal of Extracellular Vesicles, 7(1). Co-Action Publishingمصطلحات موضوعية: 0301 basic medicine, Histology, Knowledge management, Standardization, Context (language use), Exosomes, Extracellular vesicles, ectosomes, 03 medical and health sciences, Extracellular Vesicles, 0302 clinical medicine, Research community, lcsh:QH573-671, Extracellular+Vesicles, Uncategorized, business.industry, lcsh:Cytology, Cell Biology, Extracellular vesicle, extracellular RNA, 3. Good health, 030104 developmental biology, extracellular vesicle function, 030220 oncology & carcinogenesis, oncosomes, business, microvesicles, Extracellular RNA, Research Article
الوصف: The discovery that extracellular vesicles (EVs) can transfer functional extracellular RNAs (exRNAs) between cells opened new avenues into the study of EVs in health and disease. Growing interest in EV RNAs and other forms of exRNA has given rise to research programmes including but not limited to the Extracellular RNA Communication Consortium (ERCC) of the US National Institutes of Health. In 2017, the International Society for Extracellular Vesicles (ISEV) administered a survey focusing on EVs and exRNA to canvass-related views and perceived needs of the EV research community. Here, we report the results of this survey. Overall, respondents emphasized opportunities for technical developments, unraveling of molecular mechanisms and standardization of methodologies to increase understanding of the important roles of exRNAs in the broader context of EV science. In conclusion, although exRNA biology is a relatively recent emphasis in the EV field, it has driven considerable interest and resource commitment. The ISEV community looks forward to continuing developments in the science of exRNA and EVs, but without excluding other important molecular constituents of EVs.
وصف الملف: image/pdf
-
3
المؤلفون: Jing Zhu, Lili Gu, Sheng Wang, Fengqian Chen, Lin Zou, Wei Chao, Xiaoxuan Fan, Huang Huang, Junyun He, Yun Li, Tuoxin Cao, Junfang Wu, Rami Ahmad Shahror
المصدر: Brain, behavior, and immunity
مصطلحات موضوعية: Immunology, Encephalopathy, Inflammation, Extracellular RNA, Article, Sepsis, Mice, Behavioral Neuroscience, Neuroinflammation, medicine, Extracellular, Animals, TLR7, Innate immunity, IL-6, Behavior, Membrane Glycoproteins, Innate immune system, Microglia, Endocrine and Autonomic Systems, business.industry, Brain, MicroRNA, medicine.disease, Immunity, Innate, Mice, Inbred C57BL, MicroRNAs, medicine.anatomical_structure, Toll-Like Receptor 7, Cytokines, medicine.symptom, business
الوصف: Sepsis-associated encephalopathy (SAE) occurs in sepsis survivors and is associated with breakdown of the blood-brain barrier (BBB), brain inflammation, and neurological dysfunction. We have previously identified a group of extracellular microRNAs (ex-miRNAs), such as miR-146a-5p, that were upregulated in the plasma of septic mice and human, and capable of inducing potent pro-inflammatory cytokines and complements. Here, we established a clinically relevant mouse model of SAE and investigated the role of extracellular miRNAs and their sensor Toll-like receptor 7 (TLR7) in brain inflammation and neurological dysfunction. We observed BBB disruption and a profound neuroinflammatory responses in the brain for up to 14 days post-sepsis; these included increased pro-inflammatory cytokines production, microglial expansion, and peripheral leukocyte accumulation in the CNS. In a battery of neurobehavioral tests, septic mice displayed impairment of motor coordination and neurological function. Sepsis significantly increased plasma RNA and miRNA levels for up to 7 days, such as miR-146a-5p. Exogenously added miR-146a-5p induces innate immune responses in both cultured microglia/astrocytes and the intact brain via a TLR7-dependent manner. Moreover, mice genetically deficient of miR-146a showed reduced accumulation of monocytes and neutrophils in the brain compared to WT after sepsis. Finally, ablation of TLR7 in the TLR7-/- mice preserved BBB integrity, reduced microglial expansion and leukocyte accumulation, and attenuated GSK3β signaling in the brain, but did not improve neurobehavioral recovery following sepsis. Taken together, these data establish an important role of extracellular miRNA and TLR7 sensing in sepsis-induced brain inflammation.
-
4
المؤلفون: Caterina Nardella, Yari Ciani, Francesca Demichelis, Vera Mugoni
المصدر: Cancer Letters. 524:57-69
مصطلحات موضوعية: Male, PCA3, Cancer Research, Computational biology, Biology, Transcriptome, Extracellular Vesicles, Prostate cancer, Biomarkers, EV-RNA, exRNA, Liquid biopsy, Transcriptomics, Antigens, Neoplasm, Biomarkers, Tumor, Cell-Free Nucleic Acids, Gene Expression Regulation, Neoplastic, Humans, MicroRNAs, Prostatic Neoplasms, RNA-Seq, microRNA, medicine, Antigens, Neoplastic, Tumor, RNA, Cancer, medicine.disease, Gene Expression Regulation, Oncology, Neoplasm, Cancer biomarkers, Extracellular RNA
الوصف: Growing bodies of evidence have demonstrated that the identification of prostate cancer (PCa) biomarkers in the patients' blood and urine may remarkably improve PCa diagnosis and progression monitoring. Among diverse cancer-derived circulating materials, extracellular RNA molecules (exRNAs) represent a compelling component to investigate cancer-related alterations. Once outside the intracellular environment, exRNAs circulate in biofluids either in association with protein complexes or encapsulated inside extracellular vesicles (EVs). Notably, EV-associated RNAs (EV-RNAs) were used for the development of several assays (such as the FDA-approved Progensa Prostate Cancer Antigen 3 (PCA3 test) aiming at improving early PCa detection. EV-RNAs encompass a mixture of species, including small non-coding RNAs (e.g. miRNA and circRNA), lncRNAs and mRNAs. Several methods have been proposed to isolate EVs and relevant RNAs, and to perform RNA-Seq studies to identify potential cancer biomarkers. However, EVs in the circulation of a cancer patient include a multitude of diverse populations that are released by both cancer and normal cells from different tissues, thereby leading to a heterogeneous EV-RNA-associated transcriptional signal. Decrypting the complexity of such a composite signal is nowadays the major challenge faced in the identification of specific tumor-associated RNAs. Multiple deconvolution algorithms have been proposed so far to infer the enrichment of cancer-specific signals from gene expression data. However, novel strategies for EVs sorting and sequencing of RNA associated to single EVs populations will remarkably facilitate the identification of cancer-related molecules. Altogether, the studies summarized here demonstrate the high potential of using EV-RNA biomarkers in PCa and highlight the urgent need of improving technologies and computational approaches to characterize specific EVs populations and their relevant RNA cargo.
-
5
المؤلفون: Reiner Kunze, Silvia Fischer, Klaus T. Preissner, Hugo H. Marti, Emil Nasyrov, Monika Brosien
المصدر: Journal of Neuroinflammation, Vol 18, Iss 1, Pp 1-13 (2021)
Journal of Neuroinflammationمصطلحات موضوعية: Damp, Immunology, Ischemia/reperfusion, Inflammation, Extracellular RNA, HMGB1, Cellular and Molecular Neuroscience, Mice, TLR, medicine, Alarmins, Animals, DAMP, Receptor, RC346-429, Innate immune system, biology, Chemistry, General Neuroscience, Research, Cerebral hypoxia, PAMP, medicine.disease, Cell biology, Stroke, medicine.anatomical_structure, Neurology, Astrocytes, biology.protein, RNA, Neurology. Diseases of the nervous system, Signal transduction, medicine.symptom, Astrocyte
الوصف: Objective Astrocytes participate in the local innate immune response of the central nervous system. In response to stress such as ischemia, activated cells release endogenous factors known as damage-associated molecular patterns (DAMPs). Self-extracellular RNA (eRNA) is such a ubiquitous alarm signal. However, it is unclear whether eRNA is involved in the early acute phase of cerebral ischemia and is sufficient to sensitize astrocytes towards a DAMP or PAMP (pathogen-associated molecular pattern) reaction. Methods Pro-inflammatory activation upon eRNA stimulation was characterized in primary murine astrocyte cultures. In vivo, an experimental stroke model was used to localize and quantify eRNA in murine brain sections. Using primary cortical neurons and the mouse hippocampal neuronal cell line HT-22, neuronal RNA release upon stress conditions related to cerebral hypoxia/ischemia was analyzed. Results While low-dose eRNA alone did not promote pro-inflammatory activation of astrocytes in culture, it strongly enhanced the expression of pro-inflammatory cytokines in the presence of either Pam2CSK4, a synthetic PAMP molecule that mimics bacterial infection, or high mobility group box 1 (HMGB1), a prominent DAMP. Synergism of eRNA/Pam2CSK4 and eRNA/HMGB1 was prevented by blockage of the astroglial toll-like receptor (TLR)-2. Inhibition of NF-κB- and mitogen-activated protein kinase-dependent signaling pathways hampered eRNA/Pam2CSK4-mediated pro-inflammatory activation of astrocytes. In vivo, the amount of non-nuclear, presumably extracellular ribosomal RNA in close proximity to neurons significantly accumulated across the infarct core and peri-infarct areas that was accompanied by transcriptional up-regulation of various pro-inflammatory factors. Accordingly, the exposure of neurons to hypoxic/ischemic stress in vitro resulted in the release of eRNA, partly mediated by active cellular processes dependent on the cytosolic calcium level. Conclusion The DAMP signal eRNA can sensitize astrocytes as active players in cerebral innate immunity towards exogenous and endogenous activators of inflammation (PAMPs and DAMPs) in a synergistic manner via TLR2-NF-κB-dependent signaling mechanisms. These findings provide new insights into the pathogenesis of ischemic stroke and other inflammatory neurological disorders. Further studies will clarify whether administration of RNase in vivo may serve as an effective treatment for inflammatory brain pathologies.
-
6
المؤلفون: Cherie E Saffold, Heather H Pua, Grant K Nation
المصدر: Immunol Rev
مصطلحات موضوعية: Microvesicle, Immunology, RNA, chemical and pharmacologic phenomena, Cell Communication, Dendritic cell, biochemical phenomena, metabolism, and nutrition, Biology, Argonaute, Article, Cell biology, Extracellular Vesicles, Immune system, Immune System, microRNA, bacteria, Immunology and Allergy, Small nucleolar RNA, Extracellular RNA
الوصف: One of the hallmarks of the immune system is a dynamic landscape of cellular communication through the secretion of soluble factors, production of cell-bound ligands, and expression of surface receptors. This communication affects all aspects of immune cell behavior, integrates the responses of immune cells in tissues, and is fundamental to orchestrating effective immunity. Recent pioneering work has shown that the transfer of ribonucleic acids (RNAs) constitutes a novel mode of cellular communication. This communication involves diverse RNA species, with short noncoding RNAs especially enriched in the extracellular space. These RNAs are highly stable and selectively packaged for secretion. Transferred RNAs have functions in target cells that both mirror their cell-intrinsic roles as well as adopt novel mechanisms of action. These extracellular RNAs both impact the behavior of individual immune cells as well as participate in local and systemic immune responses. The impacts of RNA communication on immune cells and disease states have important implications for the development of novel clinical biomarkers and innovative therapeutic designs in immune-related disease. In this review, we will discuss the foundation of knowledge that is establishing RNA communication as an active and functional process in the immune system.
-
7
المؤلفون: Shin Otake, Kenji Takahashi, Mitsuyoshi Okada, Tushar Patel, Yosui Tamaki, Satoshi Fujii, Kazunobu Aso, Masakazu Haneda, Yu Ota, Irene Yan
المصدر: FEBS Open Bio
FEBS Open Bio, Vol 11, Iss 12, Pp 3276-3292 (2021)مصطلحات موضوعية: Stromal cell, Epithelial-Mesenchymal Transition, QH301-705.5, General Biochemistry, Genetics and Molecular Biology, Cholangiocarcinoma, Extracellular Vesicles, Cell Movement, Cell Line, Tumor, microRNA, Tumor Microenvironment, Humans, Neoplasm Invasiveness, Epithelial–mesenchymal transition, Biology (General), Transcription factor, Research Articles, Cell Proliferation, Tumor microenvironment, epithelial‐mesenchymal transition, Cell growth, Chemistry, RNA, Epithelial Cells, Cell biology, secretome, MicroRNAs, Gene Expression Regulation, Extracellular RNA, Research Article, Signal Transduction
الوصف: Extracellular vesicles (EV) within the cellular secretome are emerging as modulators of pathological processes involved in tumor growth through their ability to transfer donor‐derived RNA into recipient cells. While the effects of tumor and stromal cell EVs within the tumor microenvironment have been studied, less is known about the contributions of normal, nontransformed cells. We examined the impact of EVs within the cellular secretome from nonmalignant cells on transformed cell growth and behavior in cholangiocarcinoma cells. These effects were enhanced in the presence of the pro‐fibrogenic mediator TGF‐β. We identified miR‐195 as a TGF‐β responsive miRNA in normal cells that can be transferred via EV to tumor cells and regulate cell growth, invasion, and migration. The effects of miR‐195 involve modulation of the epithelial–mesenchymal transition through direct effects on the transcription factor Snail. These studies provide in vitro and in vivo evidence for the impact of normal cellular secretome on transformed cell growth, show the importance of EV RNA transfer, and identify mechanisms of EV‐mediated transfer of miRNA as a contributor to tumor development, which may provide new therapeutic opportunities for targeting human cholangiocarcinoma.
Cholangiocyte cell secretome can include extracellular vesicles (EV) containing tumor‐suppressive noncoding RNA such as miR‐195 and contribute to microenvironmental modulation of cholangiocarcinoma growth. miR‐195 can suppress the epithelial–mesenchymal transition and inhibit tumor invasion, migration, and growth. -
8
المؤلفون: Keren Levy, Bettina Fishman, Anat Barnea, Amir Ayali, Eran Tauber
المصدر: International Journal of Molecular Sciences; Volume 23; Issue 19; Pages: 11358
مصطلحات موضوعية: Inorganic Chemistry, Organic Chemistry, General Medicine, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Catalysis, Computer Science Applications, light pollution, artificial light at night, ALAN, insects, circadian rhythm, extracellular RNA
الوصف: Light is the major signal entraining the circadian clock that regulates physiological and behavioral rhythms in most organisms, including insects. Artificial Light at Night (ALAN) disrupts the natural light-dark cycle and negatively impacts animals at various levels. We simulated ALAN using dim light stimuli and tested their impact on gene expression in the cricket Gryllus bimaculatus, a model of insect physiology and chronobiology. At night, adult LD crickets were exposed for 30 minutes to a light pulse of 2-40 lx. The relative expression of five circadian clock associated genes was compared using qPCR. A dim ALAN pulse elicited tissue-dependent differential expression in some of these genes. The strongest effect was observed in the brain and in the optic lobe, the cricket’s circadian pacemaker. Expression of opsin-Long Wave (opLW) was upregulated, as well as cryptochrome1-2 (cry), and period (per). Our findings demonstrate that even a dim ALAN exposure may affect insects at the molecular level, underscoring the detrimental impact of ALAN on the circadian clock system.
وصف الملف: application/pdf
-
9
المصدر: Leukemia. 35:2771-2783
مصطلحات موضوعية: Cancer Research, business.industry, Cancer, Hematology, Computational biology, Plasma cell, medicine.disease, Genome, medicine.anatomical_structure, Oncology, Extracellular, Nucleic acid, Medicine, Liquid biopsy, business, Multiple myeloma, Extracellular RNA
الوصف: Liquid biopsies-a source of circulating cell-free nucleic acids, proteins and extracellular vesicles-are currently being explored for the quantitative and qualitative characterisation of the tumour genome and as a mode of non-invasive therapeutic monitoring in cancer. Emerging data suggest that liquid biopsies might offer a potentially simple, non-invasive, repeatable strategy for diagnosis, prognostication and therapeutic decision making in a genetically heterogeneous disease like multiple myeloma (MM), with particular applicability in subsets of patients where conventional markers of disease burden may be less informative. In this review, we describe the emerging utility of the evaluation of circulating tumour DNA, extracellular RNA, cell-free proteins and metabolites and extracellular vesicles in MM.
-
10
المؤلفون: Kenneth W. Witwer, Juan Pablo Tosar, Alfonso Cayota
المصدر: Trends Biochem Sci
مصطلحات موضوعية: 0303 health sciences, Chemistry, RNA, Cell Communication, Biochemistry, Article, Microvesicles, Cell biology, Extracellular Vesicles, MicroRNAs, 03 medical and health sciences, 0302 clinical medicine, microRNA, Extracellular, Humans, Molecular Biology, 030217 neurology & neurosurgery, Biogenesis, Function (biology), Intracellular, 030304 developmental biology, Extracellular RNA
الوصف: It is assumed that RNAs enriched in extracellular samples were selected for release by their parental cells. However, recent descriptions of extracellular RNA (exRNA) biogenesis and their differential stabilities question this assumption, as they could produce identical outcomes. Here, we share our opinion about the importance of considering both selective and nonselective mechanisms for RNA release into the extracellular environment. In doing so, we provide new perspectives on RNA-mediated intercellular communication, including an analogy to communication through social media. We also argue that technical limitations have restricted the study of some of the most abundant exRNAs, both inside and outside extracellular vesicles (EVs). These RNAs may be better positioned to induce a response in recipient cells compared with low abundance microRNAs.
إعادة تعيين المنقحات
عرض المنقحات (%%عد%%)
Full Text via ClinicalKey 
Find this article in full text from Springer Verlag.