Non-coding RNA derived from extracellular vesicles in cancer immune escape: Biological functions and potential clinical applications

Osteosarcoma is the most common bone tumor affecting both adolescents and children. Although localized osteosarcoma has an overall survival of >70% in the clinic, metastatic, refractory, and recurrent osteosarcoma have poorer survival rates. Exosomes are extracellular vesicles released by cells and originally thought to be a way for cells to discard unwanted products. Currently, exosomes have been reported to be involved in intercellular cross-talk and induce changes in cellular behavior by transferring cargoes (proteins, DNA, RNA, and lipids) between cells. Exosomes regulate osteosarcoma progression, and processes such as tumorigenesis, proliferation, metastasis, angiogenesis, immune evasion, and drug resistance. Increasing evidences shows that exosomes have significant potential in promoting osteosarcoma progression and development. In this review, we describe the current research status of exosomes in osteosarcoma, focusing on the biological functions of osteosarcoma exosomes as well as their application in osteosarcoma as diagnostic biomarkers and therapeutic targets.

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Extracellular Vesicles and Tumor-Immune Escape: Biological Functions and Clinical Perspectives

International Journal of Molecular Sciences ◽

10.3390/ijms21072286 ◽

2020 ◽

Vol 21 (7) ◽

pp. 2286 ◽

Cited By ~ 8

Author(s):

Stefania Raimondo ◽

Marzia Pucci ◽

Riccardo Alessandro ◽

Simona Fontana

Keyword(s):

Cancer Cells ◽

Extracellular Vesicles ◽

Immune Cell ◽

Immune Escape ◽

Immune Checkpoints ◽

Cancer Therapies ◽

Biological Functions ◽

Hallmarks Of Cancer ◽

Tumor Immune Escape

The modulation of the immune system is one of the hallmarks of cancer. It is now widely described that cancer cells are able to evade the immune response and thus establish immune tolerance. The exploration of the mechanisms underlying this ability of cancer cells has always attracted the scientific community and is the basis for the development of new promising cancer therapies. Recent evidence has highlighted how extracellular vesicles (EVs) represent a mechanism by which cancer cells promote immune escape by inducing phenotypic changes on different immune cell populations. In this review, we will discuss the recent findings on the role of tumor-derived extracellular vesicles (TEVs) in regulating immune checkpoints, focusing on the PD-L1/PD-1 axis.

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Extracellular Vesicles in Human Milk

Pharmaceuticals ◽

10.3390/ph14101050 ◽

2021 ◽

Vol 14 (10) ◽

pp. 1050

Author(s):

Yong Hu ◽

Johannes Thaler ◽

Rienk Nieuwland

Keyword(s):

Human Milk ◽

Extracellular Vesicles ◽

Blood Clotting ◽

Current Knowledge ◽

Bovine Milk ◽

Clinical Applications ◽

Biological Functions ◽

Gastrointestinal Conditions ◽

Coagulant Activity

Milk supports the growth and development of infants. An increasing number of mostly recent studies have demonstrated that milk contains a hitherto undescribed component called extracellular vesicles (EVs). This presents questions regarding why milk contains EVs and what their function is. Recently, we showed that EVs in human milk expose tissue factor, the protein that triggers coagulation or blood clotting, and that milk-derived EVs promote coagulation. Because bovine milk, which also contains EVs, completely lacks this coagulant activity, important differences are present in the biological functions of human milk-derived EVs between species. In this review, we will summarize the current knowledge regarding the presence and biochemical composition of milk EVs, their function(s) and potential clinical applications such as in probiotics, and the unique problems that milk EVs encounter in vivo, including survival of the gastrointestinal conditions encountered in the newborn. The main focus of this review will be human milk-derived EVs, but when available, we will also include information regarding non-human milk for comparison.

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Extracellular Vesicles in Lung Cancer: Prospects for Diagnostic and Therapeutic Applications

Cancers ◽

10.3390/cancers13184604 ◽

2021 ◽

Vol 13 (18) ◽

pp. 4604

Author(s):

Taketo Kato ◽

Jody V. Vykoukal ◽

Johannes F. Fahrmann ◽

Samir Hanash

Keyword(s):

Lung Cancer ◽

Extracellular Vesicles ◽

Clinical Utility ◽

Tumor Development ◽

Clinical Applications ◽

Biological Functions ◽

Therapeutic Targeting ◽

Therapeutic Applications ◽

Isolation Methods ◽

Mesenchymal Transformation

Extracellular vesicles (EVs) are nano-sized lipid-bound particles containing proteins, nucleic acids and metabolites released by cells. They have been identified in body fluids including blood, saliva, sputum and pleural effusions. In tumors, EVs derived from cancer and immune cells mediate intercellular communication and exchange, and can affect immunomodulatory functions. In the context of lung cancer, emerging evidence implicates EV involvement during various stages of tumor development and progression, including angiogenesis, epithelial to mesenchymal transformation, immune system suppression, metastasis and drug resistance. Additionally, tumor-derived EVs (TDEs) have potential as a liquid biopsy source and as a means of therapeutic targeting, and there is considerable interest in developing clinical applications for EVs in these contexts. In this review, we consider the biogenesis, components, biological functions and isolation methods of EVs, and the implications for their clinical utility for diagnostic and therapeutic applications in lung cancer.

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Interplay between Hypoxia and Extracellular Vesicles in Cancer and Inflammation

Biology ◽

10.3390/biology10070606 ◽

2021 ◽

Vol 10 (7) ◽

pp. 606

Author(s):

Marta Venturella ◽

Mattia Criscuoli ◽

Fabio Carraro ◽

Antonella Naldini ◽

Davide Zocco

Keyword(s):

Extracellular Vesicles ◽

Stress Condition ◽

Biological Functions ◽

Severe Stress ◽

Cancer And Inflammation

Hypoxia is a severe stress condition often observed in cancer and chronically inflamed cells and tissues. Extracellular vesicles play pivotal roles in these pathological processes and carry biomolecules that can be detected in many biofluids and may be exploited for diagnostic purposes. Several studies report the effects of hypoxia on extracellular vesicles’ release, molecular content, and biological functions in disease. This review summarizes the most recent findings in this field, highlighting the areas that warrant further investigation.

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Protein glycosylation in extracellular vesicles: Structural characterization and biological functions

Molecular Immunology ◽

10.1016/j.molimm.2021.04.017 ◽

2021 ◽

Vol 135 ◽

pp. 226-246

Author(s):

Janaina Macedo-da-Silva ◽

Verônica F. Santiago ◽

Livia Rosa-Fernandes ◽

Claudio R.F. Marinho ◽

Giuseppe Palmisano

Keyword(s):

Extracellular Vesicles ◽

Structural Characterization ◽

Protein Glycosylation ◽

Biological Functions

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The Role of Extracellular Vesicles as Shuttles of RNA and Their Clinical Significance as Biomarkers in Hepatocellular Carcinoma

Genes ◽

10.3390/genes12060902 ◽

2021 ◽

Vol 12 (6) ◽

pp. 902

Author(s):

Eva Costanzi ◽

Carolina Simioni ◽

Gabriele Varano ◽

Cinzia Brenna ◽

Ilaria Conti ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Extracellular Vesicles ◽

Tumor Metastasis ◽

Biological Processes ◽

Rna Molecules ◽

Expression Of Genes ◽

Non Coding Rna ◽

Donor Cells ◽

Relevant Role

Extracellular vesicles (EVs) have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA). Growing evidence for the enrichment of peculiar RNA species in specific EV subtypes has been demonstrated. ncRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from EVs and the methodologies used play a relevant role. In liver, EVs play a crucial role in regulating cell–cell communications and several pathophysiological events in the heterogeneous liver class of cells via horizontal transfer of their cargo. This review aims to discuss the rising role of EVs and their ncRNAs content in regulating specific aspects of hepatocellular carcinoma development, including tumorigenesis, angiogenesis, and tumor metastasis. We analyze the progress in EV-ncRNAs’ potential clinical applications as important diagnostic and prognostic biomarkers for liver conditions.

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Exosome-derived noncoding RNAs in gastric cancer: functions and clinical applications

Molecular Cancer ◽

10.1186/s12943-021-01396-6 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Xiao-Huan Tang ◽

Ting Guo ◽

Xiang-Yu Gao ◽

Xiao-Long Wu ◽

Xiao-Fang Xing ◽

...

Keyword(s):

Gastric Cancer ◽

Noncoding Rnas ◽

Tumour Microenvironment ◽

Clinical Applications ◽

Biological Molecules ◽

Biological Functions ◽

Membrane Structures ◽

Chemical Substances ◽

Expression Levels ◽

The Stability

AbstractExosomes are a subpopulation of the tumour microenvironment (TME) that transmit various biological molecules to promote intercellular communication. Exosomes are derived from nearly all types of cells and exist in all body fluids. Noncoding RNAs (ncRNAs) are among the most abundant contents in exosomes, and some ncRNAs with biological functions are specifically packaged into exosomes. Recent studies have revealed that exosome-derived ncRNAs play crucial roles in the tumorigenesis, progression and drug resistance of gastric cancer (GC). In addition, regulating the expression levels of exosomal ncRNAs can promote or suppress GC progression. Moreover, the membrane structures of exosomes protect ncRNAs from degradation by enzymes and other chemical substances, significantly increasing the stability of exosomal ncRNAs. Specific hallmarks within exosomes that can be used for exosome identification, and specific contents can be used to determine their origin. Therefore, exosomal ncRNAs are suitable for use as diagnostic and prognostic biomarkers or therapeutic targets. Regulating the biogenesis of exosomes and the expression levels of exosomal ncRNAs may represent a new way to block or eradicate GC. In this review, we summarized the origins and characteristics of exosomes and analysed the association between exosomal ncRNAs and GC development.

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Designed Synthesis of Diversely Substituted Hydantoins and Hydantoin-Based Hybrid Molecules: A Personal Account

Synlett ◽

10.1055/a-1480-6474 ◽

2021 ◽

Author(s):

Vinod Kumar

Keyword(s):

Clinical Applications ◽

Point Of View ◽

Biological Functions ◽

Personal Account ◽

Pharmacological Activities ◽

Structural Modifications ◽

Hybrid Molecules ◽

Biological Target ◽

Designed Synthesis ◽

Mixed Mechanism

Hydantoin and its analogs such as thiohydantoin and iminohydantoin have received substantial attention both from a chemical and biological point of view. Several compounds of this class have shown useful pharmacological activities such as anticonvulsant, antitumor, antiarrhythmic, herbicidal, and others that lead in some cases to clinical applications. Because of broad-spectrum activities, intensive research efforts have been dedicated in industry and academia to the synthesis and structural modifications of hydantoin and its derivatives. Realizing the importance of hydantoin in organic and medicinal chemistry, we also initiated a research program to successfully design and develop the new routes/methods resulting in the formation of hydantoin, thiohydantoin, and iminohydantoin substituted at different positions particularly at the N-1 position without following protection-deprotection strategy. Given the fact that the combination of two or more pharmacophoric groups may lead to hybrid molecules which result in a mixed mechanism of action on the biological target. We, therefore, further extended the developed strategy for the synthesis of new types of hydantoin-based hybrid molecules by combining hydantoin with a triazole, isoxazoline, and phosphate scaffolds as another pharmacophoric group to exploit diverse biological functions.

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The value of lncRNAs as prognostic biomarkers on clinical outcomes in osteosarcoma: a meta-analysis

BMC Cancer ◽

10.1186/s12885-021-07882-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Wenchao Zhang ◽

Xiaolei Ren ◽

Lin Qi ◽

Chenghao Zhang ◽

Chao Tu ◽

...

Keyword(s):

Web Of Science ◽

Meta Analysis ◽

Positive Outcome ◽

Clinical Applications ◽

Clinicopathological Features ◽

Cochrane Library ◽

Human Osteosarcoma ◽

Non Coding Rna ◽

The Cochrane Library ◽

Long Non Coding Rna

Abstract Background In recent years, emerging studies have demonstrated critical functions and potential clinical applications of long non-coding RNA (lncRNA) in osteosarcoma. To further validate the prognostic value of multiple lncRNAs, we have conducted this updated meta-analysis. Methods Literature retrieval was conducted by searching PubMed, Web of Science and the Cochrane Library (last update by October 2, 2019). A meta-analysis was performed to explore association between lncRNAs expression and overall survival (OS) of osteosarcoma patients. Relationships between lncRNAs expression and other clinicopathological features were also analyzed respectively. Results Overall, 4351 patients from 62 studies were included in this meta-analysis and 25 lncRNAs were identified. Pooled analyses showed that high expression of 14 lncRNAs connoted worse OS, while two lncRNAs were associated with positive outcome. Further, analysis toward osteosarcoma clinicopathologic features demonstrated that overexpression of TUG1 and XIST indicated poor clinical parameters of patients. Conclusions This meta-analysis has elucidated the prognostic potential of 16 lncRNAs in human osteosarcoma. Evidently, desperate expression and functional targets of these lncRNAs offer new approaches for prognosis and therapy of osteosarcoma.

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