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      Circular RNA MYLK promotes tumour growth and metastasis via modulating miR‐513a‐5p/VEGFC signalling in renal cell carcinoma

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          Abstract

          Growing evidence indicates that circular RNAs (circRNAs) are promising biomarkers, as they play significant roles in the development of various cancers. The circular RNA MYLK (circMYLK) has been reported to be involved in the development of malignant tumours, including liver, prostate and bladder cancers. Nevertheless, the biological function of circMYLK in renal cell carcinoma (RCC) remains unclear. In this study, we observed that circMYLK is notably up‐regulated in RCC. Increased circMYLK expression led to a larger tumour size, distant metastasis and poor prognosis of RCC patients. Moreover, circMYLK silencing repressed RCC growth and metastasis in vitro and in vivo. Mechanistically, circMYLK can capture miR‐513a‐5p to facilitate VEGFC expression and further promote the tumorigenesis of RCC cells. In summary, our findings demonstrate that circMYLK has an oncogenic role in RCC growth and metastasis by modulating miR‐513a‐5p/VEGFC signalling. Thus, circMYLK has potential as a diagnostic biomarker and therapeutic target in the treatment of RCC.

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          Circular RNA circTADA2A promotes osteosarcoma progression and metastasis by sponging miR-203a-3p and regulating CREB3 expression

          Background As a subclass of noncoding RNAs, circular RNAs (circRNAs) have been demonstrated to play a critical role in regulating gene expression in eukaryotes. Recent studies have revealed the pivotal functions of circRNAs in cancer progression. However, little is known about the role of circTADA2A, also named hsa_circ_0043278, in osteosarcoma (OS). Methods CircTADA2A was selected from a previously reported circRNA microarray comparing OS cell lines and normal bone cells. QRT-PCR was used to detect the expression of circTADA2A in OS tissue and cell lines. Luciferase reporter, RNA immunoprecipitation (RIP), RNA pull-down and fluorescence in situ hybridization (FISH) assays were performed to confirm the binding of circTADA2A with miR-203a-3p. OS cells were stably transfected with lentiviruses, and Transwell migration, Matrigel invasion, colony formation, proliferation, apoptosis, Western blotting, and in vivo tumorigenesis and metastasis assays were employed to evaluate the roles of circTADA2A, miR-203a-3p and CREB3. Results Our findings demonstrated that circTADA2A was highly expressed in both OS tissue and cell lines, and circTADA2A inhibition attenuated the migration, invasion and proliferation of OS cells in vitro as well as tumorigenesis and metastasis in vivo. A mechanistic study revealed that circTADA2A could readily sponge miR-203a-3p to upregulate the expression of CREB3, which was identified as a driver gene in OS. Furthermore, miR-203a-3p inhibition or CREB3 overexpression could reverse the circTADA2A silencing-induced impairment of malignant tumor behavior. Conclusions CircTADA2A functions as a tumor promoter in OS to increase malignant tumor behavior through the miR-203a-3p/CREB3 axis, which could be a novel target for OS therapy. Electronic supplementary material The online version of this article (10.1186/s12943-019-1007-1) contains supplementary material, which is available to authorized users.
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            Circular RNAs in immune responses and immune diseases

            Circular RNAs (circRNAs) are novel clusters of endogenous noncoding RNAs (ncRNAs) that are widely expressed in eukaryotic cells. In contrast to the generation of linear RNA transcripts, circRNAs undergo a “back-splicing” process to form a continuous, covalently closed, stable loop structure without 5ʹ or 3ʹ polarities and poly (A) tails during posttranscriptional modification. Due to the widespread availability of several technologies, especially high-throughput RNA sequencing, numerous circRNAs have been discovered not only in mammals but also in plants and insects. Notably, due to their abilities to serve as microRNA (miRNA) “sponges”, miRNA “reservoirs”, regulate gene expression and encode proteins, circRNAs participate in the development and progression of different immune responses and immune diseases by enriching various forms of epigenetic modification. CircRNAs have been demonstrated to be expressed in a tissue-specific and pathogenesis-related manner during the occurrence of multiple immune diseases. Additionally, because of their circular configurations, expression in blood and peripheral tissues and coexistence with exosomes, circRNAs show inherent conservation along with environmental resistance stability and may be regarded as potential biomarkers or therapeutic targets for some immune diseases. In this review, we summarize the characteristics, functions and mechanisms of circRNAs and their involvement in immune responses and diseases. Although our knowledge of circRNAs remains preliminary, this field is worthy of deeper exploration and greater research efforts.
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              Vascular endothelial growth factor C induces angiogenesis in vivo.

              Vascular endothelial growth factor C (VEGF-C) recently has been described to be a relatively specific growth factor for the lymphatic vascular system. Here we report that ectopic application of recombinant VEGF-C also has potent angiogenic effects in vivo. VEGF-C is sufficiently potent to stimulate neovascularization from limbal vessels in the mouse cornea. Similar to VEGF, the angiogenic response of corneas induced by VEGF-C is intensive, with a high density of new capillaries. However, the outgrowth of microvessels stimulated by VEGF-C was significantly longer than that induced by VEGF. In the developing embryo, VEGF-C was able to induce branch sprouts from the established blood vessels. VEGF-C also induced an elongated, spindle-like cell shape change and actin reorganization in both VEGF receptor (VEGFR)-2 and VEGFR-3-overexpressing endothelial cells, but not in VEGFR-1-expressing cells. Further, both VEGFR-2 and VEGFR-3 could mediate proliferative and chemotactic responses in endothelial cells on VEGF-C stimulation. Thus, VEGF-C may regulate physiological angiogenesis and participate in the development and progression of angiogenic diseases in addition to lymphangiogenesis.
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                Author and article information

                Contributors
                jing_yu2004@aliyun.com
                guiyaoting2007@aliyun.com
                Journal
                J Cell Mol Med
                J. Cell. Mol. Med
                10.1111/(ISSN)1582-4934
                JCMM
                Journal of Cellular and Molecular Medicine
                John Wiley and Sons Inc. (Hoboken )
                1582-1838
                1582-4934
                27 April 2020
                June 2020
                : 24
                : 12 ( doiID: 10.1111/jcmm.v24.12 )
                : 6609-6621
                Affiliations
                [ 1 ] Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics Institute of Urology Peking University Shenzhen Hospital Shenzhen‐Peking University‐the Hong Kong University of Science and Technology Medical Center Shenzhen China
                [ 2 ] Anhui Medical University Hefei China
                [ 3 ] Department of Laboratory Medicine Peking University Shenzhen Hospital Shenzhen China
                [ 4 ] Department of Urology The Affiliated Luohu Hospital of Shenzhen University Shenzhen China
                Author notes
                [*] [* ] Correspondence

                Yaoting Gui, Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen 518000, China.

                Email: guiyaoting2007@ 123456aliyun.com

                Jing Yu, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen‐Peking University‐the Hong Kong University of Science and Technology Medical Center, Shenzhen 518000, China.

                Email: jing_yu2004@ 123456aliyun.com

                Author information
                https://orcid.org/0000-0002-2595-3073
                Article
                JCMM15308
                10.1111/jcmm.15308
                7299689
                32342645
                bb35494e-6212-4426-a4cc-b25500815d1e
                © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 07 February 2020
                : 02 April 2020
                : 07 April 2020
                Page count
                Figures: 8, Tables: 1, Pages: 13, Words: 5876
                Funding
                Funded by: The Guangdong Foundation of Nature Science
                Award ID: 2020A1515010067
                Funded by: The Shenzhen Project of Science and Technology
                Award ID: JCYJ20170413100245260
                Funded by: The National Key R&D Program of China
                Award ID: 2019YFA09006003
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                June 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.4 mode:remove_FC converted:17.06.2020

                Molecular medicine
                circmylk,mir‐513a‐5p,renal cell carcinoma,therapeutic target,vegfc
                Molecular medicine
                circmylk, mir‐513a‐5p, renal cell carcinoma, therapeutic target, vegfc

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