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      Extracellular vesicles carrying miRNA-181b-5p affects the malignant progression of acute lymphoblastic leukemia

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          Abstract

          Objective

          To investigate how serum extracellular vesicles (EVs)-carried miRNA-181b-5p affected the proliferation, cell cycle and apoptosis of acute lymphoblastic leukemia (ALL) cells.

          Methods

          Differentially expressed miRNAs related to ALL were screened by bioinformatics analysis, and the localization of target miRNA was searched by its expression. qRT-PCR was adopted to confirm the expression of miRNA-181b-5p. Flow cytometry and fluorescence microscopy were applied to evaluate EVs internalization. MTT assay was employed to verify the proliferation of ALL cells. Cell cycle and apoptosis were analyzed by flow cytometry. Transwell assay was applied to evaluate migration and invasion abilities.

          Results

          High expression of miRNA-181b-5p was proved in ALL cell lines, and miRNA-181b-5p enriched in the exosomes and vesicles of blood cells. In the meantime, it was found that EVs carrying miRNA-181b-5p could be internalized by ALL cells and thus the expression of miRNA-181b-5p was up-regulated. Cell function assays showed that the proliferation, migration, invasion abilities of ALL cell lines were promoted in miRNA-181b-5p mimic group or the group co-culturing ALL-derived EVs and BALL-1 cell lines. The percentage of cells in G0/G1 phase was reduced and cell apoptosis was also inhibited.

          Conclusion

          miRNA-181b-5p carried by EVs in peripheral blood of ALL patients can enter ALL cells and thus promote the malignancy of ALL cells.

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          Most cited references24

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          Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.

          Hadi Valadi, Karin Ekström, Apostolos Bossios … (2007)
          Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called "exosomal shuttle RNA" (esRNA).
          Article 0 comments Cited 2309 times – based on 0 reviews     Review now
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            Extracellular vesicles: Exosomes, microvesicles, and friends

            Graça Raposo, Willem Stoorvogel (2013)
            Cells release into the extracellular environment diverse types of membrane vesicles of endosomal and plasma membrane origin called exosomes and microvesicles, respectively. These extracellular vesicles (EVs) represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, and RNA. Deficiencies in our knowledge of the molecular mechanisms for EV formation and lack of methods to interfere with the packaging of cargo or with vesicle release, however, still hamper identification of their physiological relevance in vivo. In this review, we focus on the characterization of EVs and on currently proposed mechanisms for their formation, targeting, and function.
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              Membrane vesicles as conveyors of immune responses.

              Clotilde Théry, Matias Ostrowski, Elodie Segura (2009)
              In multicellular organisms, communication between cells mainly involves the secretion of proteins that then bind to receptors on neighbouring cells. But another mode of intercellular communication - the release of membrane vesicles - has recently become the subject of increasing interest. Membrane vesicles are complex structures composed of a lipid bilayer that contains transmembrane proteins and encloses soluble hydrophilic components derived from the cytosol of the donor cell. These vesicles have been shown to affect the physiology of neighbouring recipient cells in various ways, from inducing intracellular signalling following binding to receptors to conferring new properties after the acquisition of new receptors, enzymes or even genetic material from the vesicles. This Review focuses on the role of membrane vesicles, in particular exosomes, in the communication between immune cells, and between tumour and immune cells.
              Article 0 comments Cited 622 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Ying Yang: sj_yangy@163.com
                Journal
                Journal ID (nlm-ta): J Transl Med
                Journal ID (iso-abbrev): J Transl Med
                Title: Journal of Translational Medicine
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1479-5876
                Publication date (Electronic): 18 December 2021
                Publication date PMC-release: 18 December 2021
                Publication date Collection: 2021
                Volume: 19
                Electronic Location Identifier: 511
                Affiliations
                [1 ]GRID grid.412467.2, ISNI 0000 0004 1806 3501, Department of Hematology, , Shengjing Hospital of China Medical University, ; Shenyang, 110000 People’s Republic of China
                [2 ]GRID grid.508137.8, ISNI 0000 0004 4914 6107, National Drug Clinical Trial Institute Office, , Qingdao Women and Children’s Hospital, ; Qingdao, China
                [3 ]Shanghai Engineering Research Center of Pharmaceutical Translation, Shanghai, China
                Article
                Publisher ID: 3174
                DOI: 10.1186/s12967-021-03174-w
                PMC ID: 8684212
                PubMed ID: 34922585
                SO-VID: 274f9e2d-cbac-4a17-a95e-258609352d6b
                Copyright © © The Author(s) 2021
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                Date received : 1 June 2021
                Date accepted : 30 November 2021
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2021

                ScienceOpen disciplines: Medicine
                Keywords: mirna-181b-5p,all,extracellular vesicles,proliferation,cell cycle
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: mirna-181b-5p, all, extracellular vesicles, proliferation, cell cycle

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