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      Long Noncoding RNA GM16343 Promotes IL-36β to Regulate Tumor Microenvironment by CD8 +T cells

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          Abstract

          Objective:

          To investigate the effect of long noncoding RNA GM16343 on interleukin 36β promotion of CD8 +T cells in tumor microenvironment regulation.

          Methods:

          The differentially expressed long noncoding RNA in interleukin 36β-stimulated mouse CD8 +T cells was screened by gene chip technology, and the significant differentially expressed long noncoding RNAs were verified by real-time polymerase chain reaction. The lentiviral vector that overexpresses or knockdown GM16343 was constructed, transfected into CD8 +T cells, and stimulated with interleukin 36β, and the amount of interferon γ secreted was detected by enzyme-linked immunosorbent assay. A mouse subcutaneous xenograft model that stably express interleukin 36β was established, and the tumor size and mouse survival time were observed by stimulation with CD8 +T cells overexpression or knockdown of GM16343.

          Results:

          A total of 12 long noncoding RNAs with significant differences were screened by gene chip analysis. Real-time polymerase chain reaction showed that the difference in GM16343 was larger, and the difference between the groups was observed to be the most significant. Compared to control group, CD8 +T cells overexpressing GM16343 increased the secretion of interferon γ, and the tumor diameter of the mice after stimulation showed significant reduction, and the survival time showed significant prolongation. Compared to control group, the CD8 +T cells after GM16343 were knocked down. The interferon γ secretion was decreased, and no significant change in tumor diameter and survival time was observed.

          Conclusion:

          Interleukin 36β may enhance antitumor immune response of CD8 +T cells by regulating GM16343.

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          Most cited references25

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          A long noncoding RNA mediates both activation and repression of immune response genes.

          An inducible program of inflammatory gene expression is central to antimicrobial defenses. This response is controlled by a collaboration involving signal-dependent activation of transcription factors, transcriptional co-regulators, and chromatin-modifying factors. We have identified a long noncoding RNA (lncRNA) that acts as a key regulator of this inflammatory response. Pattern recognition receptors such as the Toll-like receptors induce the expression of numerous lncRNAs. One of these, lincRNA-Cox2, mediates both the activation and repression of distinct classes of immune genes. Transcriptional repression of target genes is dependent on interactions of lincRNA-Cox2 with heterogeneous nuclear ribonucleoprotein A/B and A2/B1. Collectively, these studies unveil a central role of lincRNA-Cox2 as a broad-acting regulatory component of the circuit that controls the inflammatory response.
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            Gene regulation in the immune system by long noncoding RNAs

            Long non-coding RNAs (lncRNAs) are being increasingly appreciated as important regulators of gene expression. Chang and colleagues review the roles identified for lncRNAs in the immune system and discuss models for how lncRNAs mediate their effects.
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              The long noncoding RNA lnc-EGFR stimulates T-regulatory cells differentiation thus promoting hepatocellular carcinoma immune evasion

              Long noncoding RNAs play a pivotal role in T-helper cell development but little is known about their roles in Treg differentiation and functions during the progression of hepatocellular carcinoma (HCC). Here, we show that lnc-epidermal growth factor receptor (EGFR) upregulation in Tregs correlates positively with the tumour size and expression of EGFR/Foxp3, but negatively with IFN-γ expression in patients and xenografted mouse models. Lnc-EGFR stimulates Treg differentiation, suppresses CTL activity and promotes HCC growth in an EGFR-dependent manner. Mechanistically, lnc-EGFR specifically binds to EGFR and blocks its interaction with and ubiquitination by c-CBL, stabilizing it and augmenting activation of itself and its downstream AP-1/NF-AT1 axis, which in turn elicits EGFR expression. Lnc-EGFR links an immunosuppressive state to cancer by promoting Treg cell differentiation, thus offering a potential therapeutic target for HCC.
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                Author and article information

                Journal
                Technol Cancer Res Treat
                Technol. Cancer Res. Treat
                TCT
                sptct
                Technology in Cancer Research & Treatment
                SAGE Publications (Sage CA: Los Angeles, CA )
                1533-0346
                1533-0338
                04 November 2019
                2019
                : 18
                : 1533033819883633
                Affiliations
                [1 ]Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
                [2 ]Jiangsu Institute of Clinical Immunology, Soochow University, Suzhou, China
                [3 ]Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou, China
                [4 ]Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology, The First Affiliated Hospital of Soochow University, Suzhou, China
                [5 ]Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China
                [6 ]Soochow University Institutes for Translational Medicine, Suzhou, China
                Author notes
                [*]Xin Zhao and Xiaoqiang Dong, Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China. Emails: zhaox@ 123456suda.edu.cn ; dongxq@ 123456hotmail.com
                Author information
                https://orcid.org/0000-0001-5430-0883
                https://orcid.org/0000-0002-4334-3228
                https://orcid.org/0000-0001-5570-6690
                Article
                10.1177_1533033819883633
                10.1177/1533033819883633
                6831968
                31684829
                0873a26a-e12f-4d3d-abef-e374ce5a49e1
                © The Author(s) 2019

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 27 July 2019
                : 02 September 2019
                : 27 September 2019
                Funding
                Funded by: Xin Zhao;
                Award ID: Gusu Health Talents Cultivation Program (GSWS20190
                Categories
                Special Collection on Local Immunity in the Tumor Microenvironment
                Original Article
                Custom metadata
                January-December 2019

                lncrna,gm16343,il-36β,colorectal cancer,tumor microenvironment,tumor immunity

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