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      New insights into the regulatory role of microRNA in tumor angiogenesis and clinical implications

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          Abstract

          Angiogenesis is essential for tumor growth and metastasis. Understanding the regulation of tumor angiogenesis has become increasingly important. MicroRNAs (miRNAs) are small noncoding RNAs that function in diverse biological processes via post-transcriptional regulation. Extensive studies have revealed two important regulatory roles of miRNAs in tumor angiogenesis: miRNAs in tumor cells affect the activity of endothelial cells via non-cell-autonomous mechanisms, and miRNAs in endothelial cells regulate the cell-autonomous behavior. Recent advances have further highlighted the role of tumor-derived extracellular vesicles in the regulation of tumor angiogenesis via transferring miRNAs to endothelial cells. In this review, we summarize the regulatory role of miRNA in tumor angiogenesis, with a highlight on clinical implications of miRNAs as biomarkers for anti-angiogenic therapy response, and as therapeutic interventions against tumor angiogenesis in vivo.

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          miR-126 regulates angiogenic signaling and vascular integrity.

          Precise regulation of the formation, maintenance, and remodeling of the vasculature is required for normal development, tissue response to injury, and tumor progression. How specific microRNAs intersect with and modulate angiogenic signaling cascades is unknown. Here, we identified microRNAs that were enriched in endothelial cells derived from mouse embryonic stem (ES) cells and in developing mouse embryos. We found that miR-126 regulated the response of endothelial cells to VEGF. Additionally, knockdown of miR-126 in zebrafish resulted in loss of vascular integrity and hemorrhage during embryonic development. miR-126 functioned in part by directly repressing negative regulators of the VEGF pathway, including the Sprouty-related protein SPRED1 and phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2/p85-beta). Increased expression of Spred1 or inhibition of VEGF signaling in zebrafish resulted in defects similar to miR-126 knockdown. These findings illustrate that a single miRNA can regulate vascular integrity and angiogenesis, providing a new target for modulating vascular formation and function.
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            Targeting microRNAs in cancer: rationale, strategies and challenges.

            MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs that regulate gene expression. Early studies have shown that miRNA expression is deregulated in cancer and experimental data indicate that cancer phenotypes can be modified by targeting miRNA expression. Based on these observations, miRNA-based anticancer therapies are being developed, either alone or in combination with current targeted therapies, with the goal to improve disease response and increase cure rates. The advantage of using miRNA approaches is based on its ability to concurrently target multiple effectors of pathways involved in cell differentiation, proliferation and survival. In this Review, we describe the role of miRNAs in tumorigenesis and critically discuss the rationale, the strategies and the challenges for the therapeutic targeting of miRNAs in cancer.
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              Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis.

              In the past several years, the importance of microRNA (miRNA) in cancer cells has been recognized. Proper control of miRNA expression is essential for maintaining a steady state of the cellular machinery. Recently, it was discovered that extracellular miRNAs circulate in the blood of both healthy and diseased patients, although ribonuclease is present in both plasma and serum. Most of the circulating miRNAs are included in lipid or lipoprotein complexes, such as apoptotic bodies, microvesicles, or exosomes, and are, therefore, highly stable. The existence of circulating miRNAs in the blood of cancer patients has raised the possibility that miRNAs may serve as a novel diagnostic marker. However, the secretory mechanism and biological function, as well as the meaning of the existence of extracellular miRNAs, remain largely unclear. In this review, we summarize the usefulness of circulating miRNA for cancer diagnosis, prognosis, and therapeutics. Furthermore, we propose a mechanism for the secretion and incorporation of miRNA into the cells. © 2010 Japanese Cancer Association.
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                Author and article information

                Contributors
                86-25-80860131 , chencheng1289@126.com
                chuxiaoyuan000@163.com
                Journal
                Mol Cancer
                Mol. Cancer
                Molecular Cancer
                BioMed Central (London )
                1476-4598
                7 February 2018
                7 February 2018
                2018
                : 17
                : 22
                Affiliations
                [1 ]ISNI 0000 0001 0115 7868, GRID grid.440259.e, Department of Medical Oncology, , Jinling Hospital, Nanjing Clinical School of Southern Medical University, ; 305 East Zhongshan Road, Nanjing, 210002 Jiangsu China
                [2 ]Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, Jiangsu 210002 China
                Article
                766
                10.1186/s12943-018-0766-4
                5804051
                29415727
                d0aa5aba-bea3-4f85-b8b4-9a43d8d02ff2
                © The Author(s). 2018

                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.

                History
                : 9 October 2017
                : 12 January 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81572457
                Award ID: 81602142
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2018

                Oncology & Radiotherapy
                tumor angiogenesis,microrna,extracellular vesicle,biomarker,mirna delivery
                Oncology & Radiotherapy
                tumor angiogenesis, microrna, extracellular vesicle, biomarker, mirna delivery

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