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      Exosomal circRNA: emerging insights into cancer progression and clinical application potential

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          Abstract

          Exosomal circRNA serves a novel genetic information molecule, facilitating communication between tumor cells and microenvironmental cells, such as immune cells, fibroblasts, and other components, thereby regulating critical aspects of cancer progression including immune escape, tumor angiogenesis, metabolism, drug resistance, proliferation and metastasis. Interestingly, microenvironment cells have new findings in influencing tumor progression and immune escape mediated by the release of exosomal circRNA. Given the intrinsic stability, abundance, and broad distribution of exosomal circRNAs, they represent excellent diagnostic and prognostic biomarkers for liquid biopsy. Moreover, artificially synthesized circRNAs may open up new possibilities for cancer therapy, potentially bolstered by nanoparticles or plant exosome delivery strategies. In this review, we summarize the functions and underlying mechanisms of tumor cell and non-tumor cell-derived exosomal circRNAs in cancer progression, with a special focus on their roles in tumor immunity and metabolism. Finally, we examine the potential application of exosomal circRNAs as diagnostic biomarkers and therapeutic targets, highlighting their promise for clinical use.

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          Most cited references187

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          The biology, function, and biomedical applications of exosomes

          The study of extracellular vesicles (EVs) has the potential to identify unknown cellular and molecular mechanisms in intercellular communication and in organ homeostasis and disease. Exosomes, with an average diameter of ~100 nanometers, are a subset of EVs. The biogenesis of exosomes involves their origin in endosomes, and subsequent interactions with other intracellular vesicles and organelles generate the final content of the exosomes. Their diverse constituents include nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their cell of origin. In various diseases, exosomes offer a window into altered cellular or tissue states, and their detection in biological fluids potentially offers a multicomponent diagnostic readout. The efficient exchange of cellular components through exosomes can inform their applied use in designing exosome-based therapeutics.
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            VEGF in Signaling and Disease: Beyond Discovery and Development

            The discovery of vascular endothelial-derived growth factor (VEGF) has revolutionized our understanding of vasculogenesis and angiogenesis during development and physiological homeostasis. Over a short span of two decades, our understanding of the molecular mechanisms by which VEGF coordinates neurovascular homeostasis has become more sophisticated. The central role of VEGF in the pathogenesis of diverse cancers and blinding eye diseases has also become evident. Elucidation of the molecular regulation of VEGF and the transformative development of multiple therapeutic pathways targeting VEGF directly or indirectly is a powerful case study of how fundamental research can guide innovation and translation. It is also an elegant example of how agnostic discovery and can transform our understanding of human disease. This review will highlight critical nodal points in VEGF biology including recent developments in immunotherapy for cancer and multi-target approaches in neovascular eye disease.
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              The Biogenesis, Functions, and Challenges of Circular RNAs

              Covalently closed circular RNAs (circRNAs) are produced by precursor mRNA back-splicing of exons of thousands of genes in eukaryotes. circRNAs are generally expressed at low levels and often exhibit cell-type-specific and tissue-specific patterns. Recent studies have shown that their biogenesis requires spliceosomal machinery and can be modulated by both cis complementary sequences and protein factors. The functions of most circRNAs remain largely unexplored, but known functions include sequestration of microRNAs or proteins, modulation of transcription and interference with splicing, and even translation to produce polypeptides. However, challenges exist at multiple levels to understanding of the regulation of circRNAs because of their circular conformation and sequence overlap with linear mRNA counterparts. In this review, we survey the recent progress on circRNA biogenesis and function and discuss technical obstacles in circRNA studies.
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                Author and article information

                Contributors
                yym@wjrmyy.cn
                icls@ujs.edu.cn
                Journal
                J Hematol Oncol
                J Hematol Oncol
                Journal of Hematology & Oncology
                BioMed Central (London )
                1756-8722
                26 June 2023
                26 June 2023
                2023
                : 16
                : 67
                Affiliations
                [1 ]GRID grid.440785.a, ISNI 0000 0001 0743 511X, Aoyang Institute of Cancer, Affiliated Aoyang Hospital of Jiangsu University, ; 279 Jingang Road, Zhangjiagang, Suzhou, 215600 Jiangsu People’s Republic of China
                [2 ]GRID grid.440785.a, ISNI 0000 0001 0743 511X, Department of Laboratory Medicine, , Wujin Hospital Affiliated with Jiangsu University, ; No. 2 North Yongning Road, Changzhou, 213017 Jiangsu People’s Republic of China
                [3 ]GRID grid.440785.a, ISNI 0000 0001 0743 511X, Zhenjiang Key Laboratory of High Technology Research on sEVs Foundation and Transformation Application, School of Medicine, , Jiangsu University, ; 301 Xuefu Road, Zhenjiang, 212013 Jiangsu People’s Republic of China
                Article
                1452
                10.1186/s13045-023-01452-2
                10294326
                37365670
                cf6a7af1-b4c9-42d6-aef8-3ab28f5c7255
                © The Author(s) 2023

                Open Access This 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
                : 23 February 2023
                : 10 May 2023
                Categories
                Review
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2023

                Oncology & Radiotherapy
                exosome,circrna,tumor immunity,tumor metabolism,biomarker,cancer therapy
                Oncology & Radiotherapy
                exosome, circrna, tumor immunity, tumor metabolism, biomarker, cancer therapy

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