scholarly journals The biology and function of extracellular vesicles in nasopharyngeal carcinoma (Review)

Author(s):  
Bo You ◽  
Ying Shan ◽  
Lili Bao ◽  
Jing Chen ◽  
Liu Yang ◽  
...  
Author(s):  
Birte Weber ◽  
Niklas Franz ◽  
Ingo Marzi ◽  
Dirk Henrich ◽  
Liudmila Leppik

AbstractDue to the continued high incidence and mortality rate worldwide, there is a need to develop new strategies for the quick, precise, and valuable recognition of presenting injury pattern in traumatized and poly-traumatized patients. Extracellular vesicles (EVs) have been shown to facilitate intercellular communication processes between cells in close proximity as well as distant cells in healthy and disease organisms. miRNAs and proteins transferred by EVs play biological roles in maintaining normal organ structure and function under physiological conditions. In pathological conditions, EVs change the miRNAs and protein cargo composition, mediating or suppressing the injury consequences. Therefore, incorporating EVs with their unique protein and miRNAs signature into the list of promising new biomarkers is a logical next step. In this review, we discuss the general characteristics and technical aspects of EVs isolation and characterization. We discuss results of recent in vitro, in vivo, and patients study describing the role of EVs in different inflammatory diseases and traumatic organ injuries. miRNAs and protein signature of EVs found in patients with acute organ injury are also debated.


Biology ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 29
Author(s):  
Raghubendra Singh Dagur ◽  
Moses New-Aaron ◽  
Murali Ganesan ◽  
Weimin Wang ◽  
Svetlana Romanova ◽  
...  

Background: Alcohol abuse is common in people living with HIV-1 and dramaticallyenhances the severity of HIV-induced liver damage by inducing oxidative stress and lysosomaldysfunction in the liver cells. We hypothesize that the increased release of extracellular vesicles(EVs) in hepatocytes and liver humanized mouse model is linked to lysosome dysfunction. Methods:The study was performed on primary human hepatocytes and human hepatoma RLWXP-GFP (Huh7.5 cells stably transfected with CYP2E1 and XPack-GFP) cells and validated on ethanol-fed liverhumanizedfumarylacetoacetate hydrolase (Fah)-/-, Rag2-/-, common cytokine receptor gamma chainknockout (FRG-KO) mice. Cells and mice were infected with HIV-1ADA virus. Results: We observedan increase in the secretion of EVs associated with a decrease in lysosomal activity and expressionof lysosomal-associated membrane protein 1. Next-generation RNA sequencing of primary humanhepatocytes revealed 63 differentially expressed genes, with 13 downregulated and 50 upregulatedgenes in the alcohol–HIV-treated group. Upstream regulator analysis of differentially expressedgenes through Ingenuity Pathway Analysis identified transcriptional regulators affecting downstreamgenes associated with increased oxidative stress, lysosomal associated disease, and function andEVs biogenesis. Our in vitro findings were corroborated by in vivo studies on human hepatocytetransplantedhumanized mice, indicating that intensive EVs’ generation by human hepatocytes andtheir secretion to serum was associated with increased oxidative stress and reduction in lysosomalactivities triggered by HIV infection and ethanol diet. Conclusion: HIV-and-ethanol-metabolisminducedEVs release is tightly controlled by lysosome status in hepatocytes and participates in thedevelopment of double-insult-induced liver injury.


2020 ◽  
Author(s):  
Chunying Luo ◽  
Min Liu ◽  
Jianwei Zhang ◽  
Guoqiang Su ◽  
Zhonghua Wei

Abstract Background: Many studies have shown that microRNAs play key functions in nasopharyngeal carcinoma proliferation, invasion and metastasis. However, whether the dysregulated level of miRNAs contributes to the metabolic shift in nasopharyngeal carcinoma is not completely understood.Objectives: This study was conducted to explore the expression and function of miR-206 in nasopharyngeal carcinoma.Methods: miR-206 expression level was examined by real-time PCR. miR-206 inhibitor, mimics, and scrambled control were transiently transfected into nasopharyngeal carcinoma cells and their effects on colony formation, glucose uptake, and lactate secretion were observed in vitro. Moreover, the relationship between the levels of miR-206 and HK2 was examined by luciferase reporter and assay western blot.Results: In our study, we reported downregulation of miR-206 expression leads to metabolic change in nasopharyngeal carcinoma cells. miR-206 controls this function by enhancing HK2 expression. The enhancement of aerobic metabolism activity induced by miR-206 leads to the rapid proliferation of nasopharyngeal carcinoma cells.Conclusions: Our data demonstrated that miR-206 was involved in the regulation of Warburg effect in nasopharyngeal carcinoma by suppressing HK2 expression.


Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1742
Author(s):  
Stefania Mantziou ◽  
Georgios S. Markopoulos

Long non-coding RNAs (lncRNAs) have emerged during the post-genomic era as significant epigenetic regulators. Viral-like 30 elements (VL30s) are a family of mouse retrotransposons that are transcribed into functional lncRNAs. Recent data suggest that VL30 RNAs are efficiently packaged in small extracellular vesicles (SEVs) through an SEV enrichment sequence. We analysed VL30 elements for the presence of the distinct 26 nt SEV enrichment motif and found that SEV enrichment is an inherent hallmark of the VL30 family, contained in 36 full-length elements, with a widespread chromosomal distribution. Among them, 25 elements represent active, present-day integrations and contain an abundance of regulatory sequences. Phylogenetic analysis revealed a recent spread of SEV-VL30s from 4.4 million years ago till today. Importantly, 39 elements contain an SFPQ-binding motif, associated with the transcriptional induction of oncogenes. Most SEV-VL30s reside in transcriptionally active regions, as characterised by their distribution adjacent to candidate cis-regulatory elements (cCREs). Network analysis of SEV-VL30-associated genes suggests a distinct transcriptional footprint associated with embryonal abnormalities and neoplasia. Given the established role of VL30s in oncogenesis, we conclude that their potential to spread through SEVs represents a novel mechanism for non-coding RNA biology with numerous implications for cellular homeostasis and disease.


2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Jacopo Meldolesi

AbstractLast century, neurons and glial cells were mostly believed to play distinct functions, relevant for the brain. Progressively, however, it became clear that neurons, astrocytes and microglia co-operate intensely with each other by release/binding of signaling factors, direct surface binding and generation/release of extracellular vesicles, the exosomes and ectosomes, called together vesicles in this abstract. The present review is focused on these vesicles, fundamental in various brain diseases. Their properties are extraordinary. The specificity of their membrane governs their fusion with distinct target cells, variable depending on the state and specificity of their cells of origin and target. Result of vesicle fusion is the discharge of their cargos into the cytoplasm of target cells. Cargos are composed of critical molecules, from proteins (various nature and function) to nucleotides (especially miRNAs), playing critical roles in immune and neurodegenerative diseases. Among immune diseases is multiple sclerosis, affected by extensive dysregulation of co-trafficking neural and glial vesicles, with distinct miRNAs inducing severe or reducing effects. The vesicle-dependent differences between progressive and relapsing-remitting forms of the disease are relevant for clinical developments. In Alzheimer’s disease the vesicles can affect the brain by changing their generation and inducing co-release of effective proteins, such Aβ and tau, from neurons and astrocytes. Specific miRNAs can delay the long-term development of the disease. Upon their traffic through the blood-brainbarrier, vesicles of various origin reach fluids where they are essential for the identification of biomarkers, important for diagnostic and therapeutic innovations, critical for the future of many brain patients.


2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Changyu Zhu ◽  
Xiaolei Jiang ◽  
Hua Xiao ◽  
Jianmei Guan

AbstractRadioresistance prevails as one of the largest obstacles in the clinical treatment of nasopharyngeal carcinoma (NPC). Meanwhile, tumor-derived extracellular vesicles (TEVs) possess the ability to manipulate radioresistance in NPC. However, its mechanism remains to be further explored. Therefore, the current study set out to explore the mechanism of microRNA (miR)-142-5p delivered by TEVs in regard to the radiosensitivity of NPC. Firstly, peripheral blood samples were collected from patients with radioresistance and radiosensitivity, followed by RT-qPCR detection of miR-142-5p expression. A dual-luciferase reporter assay was carried out to elucidate the targeting relationship of miR-142-5p with HGF and EGF. In addition, radiotherapy-resistant NPC cell models were established by screening NPC cells with gradient increasing radiation exposure, and co-incubated with EVs isolated from miR-142-5p mimic-transfected NPC cells, followed by overexpression of HGF and EGF. Moreover, cell viability was detected by means of MTS, cell proliferation with a colony formation assay, cell apoptosis with flow cytometry, and expression patterns of related genes with the help of Western blot analysis. NPC xenotransplantation models in nude mice were also established by subcutaneous injection of 5-8FR cells to determine apoptosis, tumorigenicity, and radiosensitivity in nude mice. It was found that miR-142-5p was poorly expressed in peripheral blood from NPC patients with radioresistance. Mechanistic experimentation illustrated that miR-142-5p inversely targeted HGF and EGF to inactivate the HGF/c-Met and EGF/EGFR pathways, respectively. NPC cell apoptosis was observed to be augmented, while their radioresistance and proliferation were restricted by EVs-miR-142-5p or HGF silencing, or EGF silencing. Furthermore, EVs-miR-142-5p inhibited growth and radioresistance and accelerated the apoptosis of radiotherapy-resistant NPC cells in nude mice by inhibiting the HGF/c-Met and EGF/EGFR pathways. Collectively, our findings indicated that TEVs might inhibit the HGF/c-Met and EGF/EGFR pathways by delivering miR-142-5p into radiotherapy-resistant NPC cells to enhance radiosensitivity in NPC.


2021 ◽  
Vol 22 (17) ◽  
pp. 9317
Author(s):  
Konstantinos Zifkos ◽  
Christophe Dubois ◽  
Katrin Schäfer

Extracellular vesicles (EVs) compose a heterogenous group of membrane-derived particles, including exosomes, microvesicles and apoptotic bodies, which are released into the extracellular environment in response to proinflammatory or proapoptotic stimuli. From earlier studies suggesting that EV shedding constitutes a cellular clearance mechanism, it has become evident that EV formation, secretion and uptake represent important mechanisms of intercellular communication and exchange of a wide variety of molecules, with relevance in both physiological and pathological situations. The putative role of EVs in hemostasis and thrombosis is supported by clinical and experimental studies unraveling how these cell-derived structures affect clot formation (and resolution). From those studies, it has become clear that the prothrombotic effects of EVs are not restricted to the exposure of tissue factor (TF) and phosphatidylserines (PS), but also involve multiplication of procoagulant surfaces, cross-linking of different cellular players at the site of injury and transfer of activation signals to other cell types. Here, we summarize the existing and novel clinical and experimental evidence on the role and function of EVs during arterial and venous thrombus formation and how they may be used as biomarkers as well as therapeutic vectors.


2019 ◽  
Vol 21 (1) ◽  
pp. 266 ◽  
Author(s):  
Gabriella Schiera ◽  
Carlo Maria Di Liegro ◽  
Italia Di Liegro

Most aspects of nervous system development and function rely on the continuous crosstalk between neurons and the variegated universe of non-neuronal cells surrounding them. The most extraordinary property of this cellular community is its ability to undergo adaptive modifications in response to environmental cues originating from inside or outside the body. Such ability, known as neuronal plasticity, allows long-lasting modifications of the strength, composition and efficacy of the connections between neurons, which constitutes the biochemical base for learning and memory. Nerve cells communicate with each other through both wiring (synaptic) and volume transmission of signals. It is by now clear that glial cells, and in particular astrocytes, also play critical roles in both modes by releasing different kinds of molecules (e.g., D-serine secreted by astrocytes). On the other hand, neurons produce factors that can regulate the activity of glial cells, including their ability to release regulatory molecules. In the last fifteen years it has been demonstrated that both neurons and glial cells release extracellular vesicles (EVs) of different kinds, both in physiologic and pathological conditions. Here we discuss the possible involvement of EVs in the events underlying learning and memory, in both physiologic and pathological conditions.


2019 ◽  
Vol 20 (8) ◽  
pp. 1848 ◽  
Author(s):  
Stefania Raimondo ◽  
Gianluca Giavaresi ◽  
Aurelio Lorico ◽  
Riccardo Alessandro

The development of effective nanosystems for drug delivery represents a key challenge for the improvement of most current anticancer therapies. Recent progress in the understanding of structure and function of extracellular vesicles (EVs)—specialized membrane-bound nanocarriers for intercellular communication—suggests that they might also serve as optimal delivery systems of therapeutics. In addition to carrying proteins, lipids, DNA and different forms of RNAs, EVs can be engineered to deliver specific bioactive molecules to target cells. Exploitation of their molecular composition and physical properties, together with improvement in bio-techniques to modify their content are critical issues to target them to specific cells/tissues/organs. Here, we will discuss the current developments in the field of animal and plant-derived EVs toward their potential use for delivery of therapeutic agents in different pathological conditions, with a special focus on cancer.


2019 ◽  
Vol 11 (492) ◽  
pp. eaav8521 ◽  
Author(s):  
Oscar P. B. Wiklander ◽  
Meadhbh Á. Brennan ◽  
Jan Lötvall ◽  
Xandra O. Breakefield ◽  
Samir EL Andaloussi

Extracellular vesicles (EVs) are nanometer-sized, lipid membrane–enclosed vesicles secreted by most, if not all, cells and contain lipids, proteins, and various nucleic acid species of the source cell. EVs act as important mediators of intercellular communication that influence both physiological and pathological conditions. Given their ability to transfer bioactive components and surmount biological barriers, EVs are increasingly being explored as potential therapeutic agents. EVs can potentiate tissue regeneration, participate in immune modulation, and function as potential alternatives to stem cell therapy, and bioengineered EVs can act as delivery vehicles for therapeutic agents. Here, we cover recent approaches and advances of EV-based therapies.


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