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      Exosomal circRNAs: biogenesis, effect and application in human diseases

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          Abstract

          Exosomes have emerged as critical mediators of intercellular communication, both locally and systemically, by regulating a diverse range of biological processes between cells. Circular RNA (circRNA) is a novel member of endogenous noncoding RNAs with widespread distribution and diverse cellular functions. Recently, circular RNAs have been identified for their enrichment and stability in exosomes. In this review, we outline the origin, biogenesis and function of exosomal circRNAs as well as their roles in various diseases. Although their precise roles and mechanisms of gene regulation remain largely elusive, exosomal circRNAs have potential applications as disease biomarkers and novel therapeutic targets.

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          Extracellular vesicles: Exosomes, microvesicles, and friends

          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.

            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.
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              The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited.

               ISAIAH FIDLER (2003)
              Researchers have been studying metastasis for more than 100 years, and only recently have we gained insight into the mechanisms by which metastatic cells arise from primary tumours and the reasons that certain tumour types tend to metastasize to specific organs. Stephen Paget's 1889 proposal that metastasis depends on cross-talk between selected cancer cells (the 'seeds') and specific organ microenvironments (the 'soil') still holds forth today. It is now known that the potential of a tumour cell to metastasize depends on its interactions with the homeostatic factors that promote tumour-cell growth, survival, angiogenesis, invasion and metastasis. How has this field developed over the past century, and what major breakthroughs are most likely to lead to effective therapeutic approaches?
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                Author and article information

                Contributors
                zqsun82@csu.edu.cn
                lmingzzu@163.com
                Journal
                Mol Cancer
                Mol. Cancer
                Molecular Cancer
                BioMed Central (London )
                1476-4598
                5 July 2019
                5 July 2019
                2019
                : 18
                Affiliations
                [1 ]GRID grid.412633.1, Key Clinical Laboratory of Henan Province, Department of Clinical Laboratory, , The First Affiliated Hospital of Zhengzhou University, ; Zhengzhou, 450052 Henan China
                [2 ]GRID grid.412633.1, Department of Colorectal Surgery, , The First Affiliated Hospital of Zhengzhou University, ; Zhengzhou, 450052 Henan China
                [3 ]ISNI 0000 0004 1799 3993, GRID grid.13394.3c, Department of Gastrointestinal Surgery, Affiliated Tumor Hospital, , Xinjiang Medical University, ; Ürümqi, 830011 Xinjiang China
                [4 ]ISNI 0000 0001 2189 3846, GRID grid.207374.5, Department of Pathology, The First Affiliated Hospital, , Zhengzhou University, ; Zhengzhou, 450052 Henan China
                [5 ]ISNI 0000 0001 2189 3846, GRID grid.207374.5, Department of Radiotherapy, The First Affiliated Hospital, , Zhengzhou University, ; Zhengzhou, 450052 Henan China
                [6 ]GRID grid.414011.1, Department of Cardiac surgery, , The Third People’s Hospital of Henan Province, ; Zhengzhou, 450000 Henan China
                Article
                1041
                10.1186/s12943-019-1041-z
                6610963
                31277663
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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.

                Funding
                Funded by: The National Natural Science Foundation of China
                Award ID: 81560385
                Award Recipient :
                Funded by: The Medical Scientific and Technological Research Project of Henan Province
                Award ID: 201702027
                Award Recipient :
                Funded by: Youth Innovation Fund Project of The First Affiliated Hospital of Zhengzhou University
                Award ID: YNQN2017035
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100010031, Postdoctoral Research Foundation of China;
                Award ID: 2017M610462
                Award Recipient :
                Funded by: The National Natural Science Foundation of Henan Province
                Award ID: 182300410342
                Award Recipient :
                Funded by: The Health Commission Technology Talents Overseas Training Project of Henan Province
                Award ID: 2018140
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2019

                Oncology & Radiotherapy

                tumor microenvironment, biomarker, exosomal circrna, circrna, exosome

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