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      Long non-coding RNA RUNXOR accelerates MDSC-mediated immunosuppression in lung cancer

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          Abstract

          Background

          RUNX1 overlapping RNA (RUNXOR) is a long non-coding RNA that has been indicated as a key regulator in the development of myeloid cells by targeting runt-related transcription factor 1 (RUNX1). Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells consisting of immature granulocytes and monocytes with immunosuppression. However, the impact of lncRNA RUNXOR on the development of MDSCs remains unknown.

          Methods

          Both the expressions of RUNXOR and RUNX1 in the peripheral blood were measured by qRT-PCR. Human MDSCs used in this study were isolated from tumor tissue of patients with lung cancer by FCM or induced from PBMCs of healthy donors with IL-1β + GM-CSF. Specific siRNA was used to knockdown the expression of RUNXOR in MDSCs.

          Results

          In this study, we found that the lncRNA RUNXOR was upregulated in the peripheral blood of lung cancer patients. In addition, as a target gene of RUNXOR, the expression of RUNX1 was downregulated in lung cancer patients. Finally, the expression of RUNXOR was higher in MDSCs isolated from the tumor tissues of lung cancer patients compared with cells from adjacent tissue. In addition, RUNXOR knockdown decreased Arg1 expression in MDSCs.

          Conclusions

          Based on our findings, it is illustrated that RUNXOR is significantly associated with the immunosuppression induced by MDSCs in lung cancer patients and may be a target of anti-tumor therapy.

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          Most cited references29

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          Myeloid-derived suppressor cells as regulators of the immune system.

          Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that expand during cancer, inflammation and infection, and that have a remarkable ability to suppress T-cell responses. These cells constitute a unique component of the immune system that regulates immune responses in healthy individuals and in the context of various diseases. In this Review, we discuss the origin, mechanisms of expansion and suppressive functions of MDSCs, as well as the potential to target these cells for therapeutic benefit.
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            The Nature of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment.

            Myeloid-derived suppressor cells (MDSC) are one of the major components of the tumor microenvironment. The main feature of these cells is their potent immune suppressive activity. MDSC are generated in the bone marrow and, in tumor-bearing hosts, migrate to peripheral lymphoid organs and the tumor to contribute to the formation of the tumor microenvironment. Recent findings have revealed differences in the function and fate of MDSC in the tumor and peripheral lymphoid organs. We review these findings here and, in this context, we discuss the current understanding as to the nature of these differences, the underlying mechanisms, and their potential impact on the regulation of tumor progression.
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              Arginine regulation by myeloid derived suppressor cells and tolerance in cancer: mechanisms and therapeutic perspectives.

              Patients with cancer have an impaired T-cell response that can decrease the potential therapeutic benefit of cancer vaccines and other forms of immunotherapy. L-arginine (L-Arg) is a conditionally essential amino acid that is fundamental for the function of T lymphocytes. Recent findings in tumor-bearing mice and cancer patients indicate that increased metabolism of L-Arg by myeloid derived suppressor cells (MDSCs) producing arginase I inhibits T-lymphocyte responses. Here we discuss some of the most recent concepts how MDSC expressing arginase I may regulate T-cell function in cancer and other chronic inflammatory diseases and suggest possible therapeutic interventions to overcome this inhibitory effect.
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                Author and article information

                Contributors
                jipinxinyu@163.com
                zjflmj19780723@126.com
                wangting8715@126.com
                tjj850913@163.com
                936847263@qq.com
                191109696@qq.com
                wyg1223@126.com
                13952815636@163.com
                86-511-8891-5746 , maolingxiang@aliyun.com
                xuhx@ujs.edu.cn
                86-511-8503-8301 , sjwjs@ujs.edu.cn
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                18 June 2018
                18 June 2018
                2018
                : 18
                : 660
                Affiliations
                [1 ]ISNI 0000 0001 0743 511X, GRID grid.440785.a, Department of Laboratory Medicine, The Affiliated People’s Hospital, , Jiangsu University, ; Zhenjiang, 212012 China
                [2 ]ISNI 0000 0001 0743 511X, GRID grid.440785.a, Institute of Laboratory Medicine, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, , Jiangsu University, ; Zhenjiang, China
                [3 ]ISNI 0000 0004 1764 4566, GRID grid.452509.f, Department of Laboratory Medicine, , Jiangsu Cancer Hospital, ; Nanjing, China
                Article
                4564
                10.1186/s12885-018-4564-6
                6006856
                29914443
                6a168818-7dd2-4d53-9494-2b4ab50d767d
                © 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
                : 4 January 2018
                : 30 May 2018
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Oncology & Radiotherapy
                lncrna runxor,mdscs,runx1,anti-tumor immunity,lung cancer
                Oncology & Radiotherapy
                lncrna runxor, mdscs, runx1, anti-tumor immunity, lung cancer

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