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18 pages, 3503 KiB

Open AccessArticle

Functional Intercellular Transmission of miHTT via Extracellular Vesicles: An In Vitro Proof-of-Mechanism Study

by Roberto D. V. S. Morais, Marina Sogorb-González, Citlali Bar, Nikki C. Timmer, M. Leontien Van der Bent, Morgane Wartel and Astrid Vallès

Cells 2022, 11(17), 2748; https://doi.org/10.3390/cells11172748 - 03 Sep 2022

Cited by 4 | Viewed by 2769

Abstract

Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by GAG expansion in exon 1 of the huntingtin (HTT) gene. AAV5-miHTT is an adeno-associated virus serotype 5-based vector expressing an engineered HTT-targeting microRNA (miHTT). Preclinical studies demonstrate the brain-wide spread of [...] Read more.

Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by GAG expansion in exon 1 of the huntingtin (HTT) gene. AAV5-miHTT is an adeno-associated virus serotype 5-based vector expressing an engineered HTT-targeting microRNA (miHTT). Preclinical studies demonstrate the brain-wide spread of AAV5-miHTT following a single intrastriatal injection, which is partly mediated by neuronal transport. miHTT has been previously associated with extracellular vesicles (EVs), but whether EVs mediate the intercellular transmission of miHTT remains unknown. A contactless culture system was used to evaluate the transport of miHTT, either from a donor cell line overexpressing miHTT or AAV5-miHTT transduced neurons. Transfer of miHTT to recipient (HEK-293T, HeLa, and HD patient-derived neurons) cells was observed, which significantly reduced HTT mRNA levels. miHTT was present in EV-enriched fractions isolated from culture media. Immunocytochemical and in situ hybridization experiments showed that the signal for miHTT and EV markers co-localized, confirming the transport of miHTT within EVs. In summary, we provide evidence that an engineered miRNA—miHTT—is loaded into EVs, transported across extracellular space, and taken up by neighboring cells, and importantly, that miHTT is active in recipient cells downregulating HTT expression. This represents an additional mechanism contributing to the widespread biodistribution of AAV5-miHTT. Full article

(This article belongs to the Special Issue Extracellular Vesicle-Associated Non-Coding RNAs)

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15 pages, 1961 KiB

Open AccessArticle

miR-150-5p and let-7b-5p in Blood Myeloid Extracellular Vesicles Track Cognitive Symptoms in Patients with Multiple Sclerosis

by Federica Scaroni, Caterina Visconte, Maria Serpente, Maria Teresa Golia, Martina Gabrielli, Marijn Huiskamp, Hanneke E. Hulst, Tiziana Carandini, Milena De Riz, Anna Pietroboni, Emanuela Rotondo, Elio Scarpini, Daniela Galimberti, Charlotte E. Teunissen, Maureen van Dam, Brigit A. de Jong, Chiara Fenoglio and Claudia Verderio

Cells 2022, 11(9), 1551; https://doi.org/10.3390/cells11091551 - 05 May 2022

Cited by 9 | Viewed by 3153

Abstract

Cognitive deficits strongly affect the quality of life of patients with multiple sclerosis (MS). However, no cognitive MS biomarkers are currently available. Extracellular vesicles (EVs) contain markers of parental cells and are able to pass from the brain into blood, representing a source [...] Read more.

Cognitive deficits strongly affect the quality of life of patients with multiple sclerosis (MS). However, no cognitive MS biomarkers are currently available. Extracellular vesicles (EVs) contain markers of parental cells and are able to pass from the brain into blood, representing a source of disease biomarkers. The aim of this study was to investigate whether small non-coding microRNAs (miRNAs) targeting synaptic genes and packaged in plasma EVs may reflect cognitive deficits in MS patients. Total EVs were precipitated by Exoquick from the plasma of twenty-six cognitively preserved (CP) and twenty-three cognitively impaired (CI) MS patients belonging to two independent cohorts. Myeloid EVs were extracted by affinity capture from total EVs using Isolectin B4 (IB4). Fourteen miRNAs targeting synaptic genes were selected and measured by RT-PCR in both total and myeloid EVs. Myeloid EVs from CI patients expressed higher levels of miR-150-5p and lower levels of let-7b-5p compared to CP patients. Stratification for progressive MS (PMS) and relapsing-remitting MS (RRMS) and correlation with clinical parameters suggested that these alterations might be attributable to cognitive deficits rather than disease progression. This study identifies miR-150-5p and let-7b-5p packaged in blood myeloid EVs as possible biomarkers for cognitive deficits in MS. Full article

(This article belongs to the Special Issue Extracellular Vesicle-Associated Non-Coding RNAs)

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17 pages, 2921 KiB

Open AccessArticle

miRNAs Contained in Extracellular Vesicles Cargo Contribute to the Progression of Idiopathic Pulmonary Fibrosis: An In Vitro Aproach

by Jovito Cesar Santos-Álvarez, Juan Manuel Velázquez-Enríquez, Rosendo García-Carrillo, César Rodríguez-Beas, Alma Aurora Ramírez-Hernández, Edilburga Reyes-Jiménez, Karina González-García, Armando López-Martínez, Laura Pérez-Campos Mayoral, Sergio Roberto Aguilar-Ruiz, María de los Ángeles Romero-Tlalolini, Honorio Torres-Aguilar, Luis Castro-Sánchez, Jaime Arellanes-Robledo, Verónica Rocío Vásquez-Garzón and Rafael Baltiérrez-Hoyos

Cells 2022, 11(7), 1112; https://doi.org/10.3390/cells11071112 - 25 Mar 2022

Cited by 9 | Viewed by 2975

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease. Lesions in the lung epithelium cause alterations in the microenvironment that promote fibroblast accumulation. Extracellular vesicles (EVs) transport proteins, lipids, and nucleic acids, such as microRNAs (miRNAs). The aim of this study was [...] Read more.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease. Lesions in the lung epithelium cause alterations in the microenvironment that promote fibroblast accumulation. Extracellular vesicles (EVs) transport proteins, lipids, and nucleic acids, such as microRNAs (miRNAs). The aim of this study was to characterize the differentially expressed miRNAs in the cargo of EVs obtained from the LL97 and LL29 fibroblast cell lines isolated from IPF lungs versus those derived from the CCD19 fibroblast cell line isolated from a healthy donors. We characterized EVs by ultracentrifugation, Western blotting, and dynamic light scattering. We identified miRNAs by small RNA-seq, a total of 1144 miRNAs, of which 1027 were known miRNAs; interestingly, 117 miRNAs were novel. Differential expression analysis showed that 77 miRNAs were upregulated and 68 were downregulated. In addition, pathway enrichment analyses from the Gene Ontology and Kyoto Encyclopedia of Genomes identified several miRNA target genes in the categories, cell proliferation, regulation of apoptosis, pathways in cancer, and proteoglycans in cancer. Our data reveal that miRNAs contained in EVs cargo could be helpful as biomarkers for fibrogenesis, diagnosis, and therapeutic intervention of IPF. Full article

(This article belongs to the Special Issue Extracellular Vesicle-Associated Non-Coding RNAs)

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14 pages, 1438 KiB

Open AccessArticle

Molecular Determinants for RNA Release into Extracellular Vesicles

by Marie-Luise Mosbach, Christina Pfafenrot, Elke Pogge von Strandmann, Albrecht Bindereif and Christian Preußer

Cells 2021, 10(10), 2674; https://doi.org/10.3390/cells10102674 - 06 Oct 2021

Cited by 9 | Viewed by 3520

Abstract

Extracellular vesicles (EVs) are important for intercellular communication and act as vehicles for biological material, such as various classes of coding and non-coding RNAs, a few of which were shown to selectively target into vesicles. However, protein factors, mechanisms, and sequence elements contributing [...] Read more.

Extracellular vesicles (EVs) are important for intercellular communication and act as vehicles for biological material, such as various classes of coding and non-coding RNAs, a few of which were shown to selectively target into vesicles. However, protein factors, mechanisms, and sequence elements contributing to this specificity remain largely elusive. Here, we use a reporter system that results in different types of modified transcripts to decipher the specificity determinants of RNAs released into EVs. First, we found that small RNAs are more efficiently packaged into EVs than large ones, and second, we determined absolute quantities for several endogenous RNA transcripts in EVs (U6 snRNA, U1 snRNA, Y1 RNA, and GAPDH mRNA). We show that RNA polymerase III (pol III) transcripts are more efficiently secreted into EVs compared to pol II-derived transcripts. Surprisingly, our quantitative analysis revealed no RNA accumulation in the vesicles relative to the total cellular levels, based on both overexpressed reporter transcripts and endogenous RNAs. RNA appears to be EV-associated only at low copy numbers, ranging between 0.02 and 1 molecule per EV. This RNA association may reflect internal EV encapsulation or a less tightly bound state at the vesicle surface. Full article

(This article belongs to the Special Issue Extracellular Vesicle-Associated Non-Coding RNAs)

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17 pages, 4072 KiB

Open AccessArticle

Differential Expression Pattern of Goat Uterine Fluids Extracellular Vesicles miRNAs during Peri-Implantation

by Yanshe Xie, Guangbin Liu, Xupeng Zang, Qun Hu, Chen Zhou, Yaokun Li, Dewu Liu and Linjun Hong

Cells 2021, 10(9), 2308; https://doi.org/10.3390/cells10092308 - 03 Sep 2021

Cited by 9 | Viewed by 2438

Abstract

Early pregnancy failure occurs when a mature embryo attaches to an unreceptive endometrium. During the formation of a receptive endometrium, extracellular vesicles (EVs) of the uterine fluids (UFs) deliver regulatory molecules such as small RNAs to mediate intrauterine communication between the embryo and [...] Read more.

Early pregnancy failure occurs when a mature embryo attaches to an unreceptive endometrium. During the formation of a receptive endometrium, extracellular vesicles (EVs) of the uterine fluids (UFs) deliver regulatory molecules such as small RNAs to mediate intrauterine communication between the embryo and the endometrium. However, profiling of small RNAs in goat UFs’ EVs during pregnancy recognition (day 16) has not been carried out. In this study, EVs were isolated from UFs on day 16 of the estrous cycle or gestation. They were isolated by Optiprep™ Density G radient (ODG) and verified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting. Immunostaining demonstrated that CD63 was present both in the endometrial epithelium and glandular epithelium, and stain intensity was greater in the pregnant endometrium compared to the non-pregnant endometrium. Small RNA sequencing revealed that UFs’ EVs contained numerous sRNA families and a total of 106 differentially expressed miRNAs (DEMs). Additionally, 1867 target genes of the DEMs were obtained, and miRNA–mRNA interaction networks were constructed. GO and KEGG analysis showed that miRNAs were significantly associated with the formation of a receptive endometrium and embryo implantation. In addition, the fluorescence in situ hybridization assay (FISH) showed that chi-miR-451-5p was mainly expressed in stromal cells of the endometrium and a higher level was detected in the endometrial luminal epithelium in pregnant states. Moreover, the dual-luciferase reporter assay showed that chi-miR-451-5p directly binds to PSMB8 and may play an important role in the formation of a receptive endometrium and embryo implantation. In conclusion, these results reveal that UFs’ EVs contain various small RNAs that may be vital in the formation of a receptive endometrium and embryo implantation. Full article

(This article belongs to the Special Issue Extracellular Vesicle-Associated Non-Coding RNAs)

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17 pages, 1668 KiB

Open AccessArticle

Profiling of Extracellular Small RNAs Highlights a Strong Bias towards Non-Vesicular Secretion

by Helena Sork, Mariana Conceicao, Giulia Corso, Joel Nordin, Yi Xin Fiona Lee, Kaarel Krjutskov, Jakub Orzechowski Westholm, Pieter Vader, Marie Pauwels, Roosmarijn E. Vandenbroucke, Matthew JA Wood, Samir EL Andaloussi and Imre Mäger

Cells 2021, 10(6), 1543; https://doi.org/10.3390/cells10061543 - 18 Jun 2021

Cited by 9 | Viewed by 3318

Abstract

The extracellular environment consists of a plethora of molecules, including extracellular miRNA that can be secreted in association with extracellular vesicles (EVs) or soluble protein complexes (non-EVs). Yet, interest in therapeutic short RNA carriers lies mainly in EVs, the vehicles conveying the great [...] Read more.

The extracellular environment consists of a plethora of molecules, including extracellular miRNA that can be secreted in association with extracellular vesicles (EVs) or soluble protein complexes (non-EVs). Yet, interest in therapeutic short RNA carriers lies mainly in EVs, the vehicles conveying the great majority of the biological activity. Here, by overexpressing miRNA and shRNA sequences in parent cells and using size exclusion liquid chromatography (SEC) to separate the secretome into EV and non-EV fractions, we saw that >98% of overexpressed miRNA was secreted within the non-EV fraction. Furthermore, small RNA sequencing studies of native miRNA transcripts revealed that although the abundance of miRNAs in EVs, non-EVs and parent cells correlated well (R² = 0.69–0.87), quantitatively an outstanding 96.2–99.9% of total miRNA was secreted in the non-EV fraction. Nevertheless, though EVs contained only a fraction of secreted miRNAs, these molecules were stable at 37 °C in a serum-containing environment, indicating that if sufficient miRNA loading is achieved, EVs can remain delivery-competent for a prolonged period of time. This study suggests that the passive endogenous EV loading strategy might be a relatively wasteful way of loading miRNA to EVs, and active miRNA loading approaches are needed for developing advanced EV miRNA therapies in the future. Full article

(This article belongs to the Special Issue Extracellular Vesicle-Associated Non-Coding RNAs)

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12 pages, 1107 KiB

Open AccessArticle

Extracellular Vesicles and Their miRNA Content in Amniotic and Tracheal Fluids of Fetuses with Severe Congenital Diaphragmatic Hernia Undergoing Fetal Intervention

by Isabella Fabietti, Tiago Nardi, Chiara Favero, Laura Dioni, Laura Cantone, Laura Pergoli, Mirjam Hoxha, Eva Pinatel, Fabio Mosca, Valentina Bollati and Nicola Persico

Cells 2021, 10(6), 1493; https://doi.org/10.3390/cells10061493 - 14 Jun 2021

Cited by 11 | Viewed by 2288

Abstract

Infants with congenital diaphragmatic hernia (CDH) are at high risk of postnatal mortality due to lung hypoplasia and arterial pulmonary hypertension. In severe cases, prenatal intervention by fetal endoscopic tracheal occlusion (FETO) can improve survival by accelerating lung growth. However, postnatal mortality remains [...] Read more.

Infants with congenital diaphragmatic hernia (CDH) are at high risk of postnatal mortality due to lung hypoplasia and arterial pulmonary hypertension. In severe cases, prenatal intervention by fetal endoscopic tracheal occlusion (FETO) can improve survival by accelerating lung growth. However, postnatal mortality remains in the range of about 50% despite fetal treatment, and there is currently no clear explanation for this different clinical response to FETO. We evaluated the concentration of extracellular vesicles (EVs) and associated microRNA expression in amniotic and tracheal fluids of fetuses with CDH undergoing FETO, and we examined the association between molecular findings and postnatal survival. We observed a higher count of EVs in the amniotic fluid of non-survivors and in the tracheal fluid sampled in utero at the time of reversal of tracheal occlusion, suggesting a pro-inflammatory lung reactivity that is already established in utero and that could be associated with a worse postnatal clinical course. In addition, we observed differential regulation of four EV-enclosed miRNAs (miR-379-5p, miR-889-3p; miR-223-3p; miR-503-5p) in relation to postnatal survival, with target genes possibly involved in altered lung development. Future research should investigate molecular therapeutic agents targeting differentially regulated miRNAs to normalize their expression and potentially improve clinical outcomes. Full article

(This article belongs to the Special Issue Extracellular Vesicle-Associated Non-Coding RNAs)

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Review

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16 pages, 1268 KiB

Open AccessReview

Extracellular Vesicles and MicroRNA in Myelodysplastic Syndromes

by Mathieu Meunier, David Laurin and Sophie Park

Cells 2023, 12(4), 658; https://doi.org/10.3390/cells12040658 - 19 Feb 2023

Cited by 1 | Viewed by 2040

Abstract

The bone marrow niche plays an increasing role in the pathophysiogenesis of myelodysplastic syndromes. More specifically, mesenchymal stromal cells, which can secrete extracellular vesicles and their miRNA contents, modulate the fate of hematopoietic stem cells leading to leukemogenesis. Extracellular vesicles can mediate their [...] Read more.

The bone marrow niche plays an increasing role in the pathophysiogenesis of myelodysplastic syndromes. More specifically, mesenchymal stromal cells, which can secrete extracellular vesicles and their miRNA contents, modulate the fate of hematopoietic stem cells leading to leukemogenesis. Extracellular vesicles can mediate their miRNA and protein contents between nearby cells but also in the plasma of the patients, being potent tools for diagnosis and prognostic markers in MDS. They can be targeted by antisense miRNA or by modulators of the secretion of extracellular vesicles and could lead to future therapeutic directions in MDS. Full article

(This article belongs to the Special Issue Extracellular Vesicle-Associated Non-Coding RNAs)

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19 pages, 1308 KiB

Open AccessFeature PaperReview

Exosome-Associated circRNAs as Key Regulators of EMT in Cancer

by Laura Amicone, Alessandra Marchetti and Carla Cicchini

Cells 2022, 11(10), 1716; https://doi.org/10.3390/cells11101716 - 23 May 2022

Cited by 9 | Viewed by 2639

Abstract

Epithelial-to-mesenchymal transition (EMT) is a dynamic program of cell plasticity aberrantly reactivated in cancer. The crosstalk between tumor cells and the tumoral microenvironment (TME) has a pivotal importance for the induction of the EMT and the progression toward a malignant phenotype. Notably, exosomes [...] Read more.

Epithelial-to-mesenchymal transition (EMT) is a dynamic program of cell plasticity aberrantly reactivated in cancer. The crosstalk between tumor cells and the tumoral microenvironment (TME) has a pivotal importance for the induction of the EMT and the progression toward a malignant phenotype. Notably, exosomes are key mediators of this crosstalk as vehicles of specific molecular signals that include the class of circular RNAs (circRNAs). This review specifically focuses on the role of exosome-associated circRNAs as key regulators of EMT in cancer. The relevance of these molecules in regulating the intercellular communication in TME and tumor progression is highlighted. Moreover, the here-presented evidence indicates that exosome-associated circRNA modulation should be taken in account for cancer diagnostic and therapeutic approaches. Full article

(This article belongs to the Special Issue Extracellular Vesicle-Associated Non-Coding RNAs)

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14 pages, 1837 KiB

Open AccessReview

The Role of Matrix-Bound Extracellular Vesicles in the Regulation of Endochondral Bone Formation

by Barbara D. Boyan, Niels C. Asmussen, Zhao Lin and Zvi Schwartz

Cells 2022, 11(10), 1619; https://doi.org/10.3390/cells11101619 - 12 May 2022

Cited by 15 | Viewed by 2560

Abstract

Matrix vesicles are key players in the development of the growth plate during endochondral bone formation. They are involved in the turnover of the extracellular matrix and its mineralization, as well as being a vehicle for chondrocyte communication and regulation. These extracellular organelles [...] Read more.

Matrix vesicles are key players in the development of the growth plate during endochondral bone formation. They are involved in the turnover of the extracellular matrix and its mineralization, as well as being a vehicle for chondrocyte communication and regulation. These extracellular organelles are released by the cells and are anchored to the matrix via integrin binding to collagen. The exact function and makeup of the vesicles are dependent on the zone of the growth plate in which they are produced. Early studies defined their role as sites of initial calcium phosphate deposition based on the presence of crystals on the inner leaflet of the membrane and subsequent identification of enzymes, ion transporters, and phospholipid complexes involved in mineral formation. More recent studies have shown that they contain small RNAs, including microRNAs, that are distinct from the parent cell, raising the hypothesis that they are a distinct subset of exosomes. Matrix vesicles are produced under complex regulatory pathways, which include the action of steroid hormones. Once in the matrix, their maturation is mediated by the action of secreted hormones. How they convey information to cells, either through autocrine or paracrine actions, is now being elucidated. Full article

(This article belongs to the Special Issue Extracellular Vesicle-Associated Non-Coding RNAs)

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26 pages, 1502 KiB

Open AccessReview

The Role of Non-Coding RNAs in the Human Placenta

by Milena Žarković, Franziska Hufsky, Udo R. Markert and Manja Marz

Cells 2022, 11(9), 1588; https://doi.org/10.3390/cells11091588 - 09 May 2022

Cited by 11 | Viewed by 2884

Abstract

Non-coding RNAs (ncRNAs) play a central and regulatory role in almost all cells, organs, and species, which has been broadly recognized since the human ENCODE project and several other genome projects. Nevertheless, a small fraction of ncRNAs have been identified, and in the [...] Read more.

Non-coding RNAs (ncRNAs) play a central and regulatory role in almost all cells, organs, and species, which has been broadly recognized since the human ENCODE project and several other genome projects. Nevertheless, a small fraction of ncRNAs have been identified, and in the placenta they have been investigated very marginally. To date, most examples of ncRNAs which have been identified to be specific for fetal tissues, including placenta, are members of the group of microRNAs (miRNAs). Due to their quantity, it can be expected that the fairly larger group of other ncRNAs exerts far stronger effects than miRNAs. The syncytiotrophoblast of fetal origin forms the interface between fetus and mother, and releases permanently extracellular vesicles (EVs) into the maternal circulation which contain fetal proteins and RNA, including ncRNA, for communication with neighboring and distant maternal cells. Disorders of ncRNA in placental tissue, especially in trophoblast cells, and in EVs seem to be involved in pregnancy disorders, potentially as a cause or consequence. This review summarizes the current knowledge on placental ncRNA, their transport in EVs, and their involvement and pregnancy pathologies, as well as their potential for novel diagnostic tools. Full article

(This article belongs to the Special Issue Extracellular Vesicle-Associated Non-Coding RNAs)

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14 pages, 1690 KiB

Open AccessReview

Molecular Mediators of RNA Loading into Extracellular Vesicles

by Chiara Corrado, Maria Magdalena Barreca, Chiara Zichittella, Riccardo Alessandro and Alice Conigliaro

Cells 2021, 10(12), 3355; https://doi.org/10.3390/cells10123355 - 30 Nov 2021

Cited by 30 | Viewed by 3106

Abstract

In the last decade, an increasing number of studies have demonstrated that non-coding RNA (ncRNAs) cooperate in the gene regulatory networks with other biomolecules, including coding RNAs, DNAs and proteins. Among them, microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are [...] Read more.

In the last decade, an increasing number of studies have demonstrated that non-coding RNA (ncRNAs) cooperate in the gene regulatory networks with other biomolecules, including coding RNAs, DNAs and proteins. Among them, microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are involved in transcriptional and translation regulation at different levels. Intriguingly, ncRNAs can be packed in vesicles, released in the extracellular space, and finally internalized by receiving cells, thus affecting gene expression also at distance. This review focuses on the mechanisms through which the ncRNAs can be selectively packaged into extracellular vesicles (EVs). Full article

(This article belongs to the Special Issue Extracellular Vesicle-Associated Non-Coding RNAs)

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18 pages, 1465 KiB

Open AccessReview

Role of Extracellular Vesicle-Based Cell-to-Cell Communication in Multiple Myeloma Progression

by Ilaria Saltarella, Aurelia Lamanuzzi, Benedetta Apollonio, Vanessa Desantis, Giulia Bartoli, Angelo Vacca and Maria Antonia Frassanito

Cells 2021, 10(11), 3185; https://doi.org/10.3390/cells10113185 - 16 Nov 2021

Cited by 16 | Viewed by 2644

Abstract

Multiple myeloma (MM) progression closely depends on the bidirectional crosstalk between tumor cells and the surrounding microenvironment, which leads to the creation of a tumor supportive niche. Extracellular vesicles (EVs) have emerged as key players in the pathological interplay between the malignant clone [...] Read more.

Multiple myeloma (MM) progression closely depends on the bidirectional crosstalk between tumor cells and the surrounding microenvironment, which leads to the creation of a tumor supportive niche. Extracellular vesicles (EVs) have emerged as key players in the pathological interplay between the malignant clone and near/distal bone marrow (BM) cells through their biologically active cargo. Here, we describe the role of EVs derived from MM and BM cells in reprogramming the tumor microenvironment and in fostering bone disease, angiogenesis, immunosuppression, drug resistance, and, ultimately, tumor progression. We also examine the emerging role of EVs as new therapeutic agents for the treatment of MM, and their potential use as clinical biomarkers for early diagnosis, disease classification, and therapy monitoring. Full article

(This article belongs to the Special Issue Extracellular Vesicle-Associated Non-Coding RNAs)

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16 pages, 910 KiB

Open AccessReview

Extracellular Vesicle Associated Non-Coding RNAs in Lung Infections and Injury

by Zhi Hao Kwok, Kareemah Ni and Yang Jin

Cells 2021, 10(5), 965; https://doi.org/10.3390/cells10050965 - 21 Apr 2021

Cited by 12 | Viewed by 2803

Abstract

Extracellular vesicles (EVs) refer to a heterogenous population of membrane-bound vesicles that are released by cells under physiological and pathological conditions. The detection of EVs in the majority of the bodily fluids, coupled with their diverse cargo comprising of DNA, RNA, lipids, and [...] Read more.

Extracellular vesicles (EVs) refer to a heterogenous population of membrane-bound vesicles that are released by cells under physiological and pathological conditions. The detection of EVs in the majority of the bodily fluids, coupled with their diverse cargo comprising of DNA, RNA, lipids, and proteins, have led to the accumulated interests in leveraging these nanoparticles for diagnostic and therapeutic purposes. In particular, emerging studies have identified enhanced levels of a wide range of specific subclasses of non-coding RNAs (ncRNAs) in EVs, thereby suggesting the existence of highly selective and regulated molecular processes governing the sorting of these RNAs into EVs. Recent studies have also illustrated the functional relevance of these enriched ncRNAs in a variety of human diseases. This review summarizes the current state of knowledge on EV-ncRNAs, as well as their functions and significance in lung infection and injury. As a majority of the studies on EV-ncRNAs in lung diseases have focused on EV-microRNAs, we will particularly highlight the relevance of these molecules in the pathophysiology of these conditions, as well as their potential as novel biomarkers therein. We also outline the current challenges in the EV field amidst the tremendous efforts to propel the clinical utility of EVs for human diseases. The lack of published literature on the functional roles of other EV-ncRNA subtypes may in turn provide new avenues for future research to exploit their feasibility as novel diagnostic and therapeutic targets in human diseases. Full article

(This article belongs to the Special Issue Extracellular Vesicle-Associated Non-Coding RNAs)

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