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      Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate gastric cancer progression

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          Abstract

          Background

          Long noncoding RNAs (lncRNAs) have recently emerged as important regulators in governing fundamental biological processes, and many of which are likely to have functional roles in tumorigenesis. Maternally expressed gene 3 (MEG3) gene encodes a lncRNA whose expression is lost in an expanding list of primary human tumors and tumor cell lines, however its biological role and regulatory mechanism in gastric cancer (GC) development and progression are poorly defined.

          Methods

          Quantitative RT-PCR analysis was used to determine whether aberrant MEG3 expression was associated with GC patients pTNM stage and pM state. Furthermore, the effect of ectopic expression of MEG3 on cell proliferation, migration, invasion and cell apoptosis was assessed by using CCK-8, wound healing, transwell invasion assays and flow cytometric analysis, respectively, in GC cell lines HGC-27 and MGC-803. Moreover, the competing endogenous RNA (ceRNA) activity of MEG3 on miR-181a was investigated via luciferase reporter assay and immunoblot analysis.

          Results

          MEG3 is decreased in GC patients and cell lines, and its expression was associated with metastatic GC. Furthermore, ectopic expression of MEG3 in HGC-27 and MGC-803 cells inhibited cell proliferation, migration, invasion, and promoted cell apoptosis, which might be due to MEG3 sequestering oncogenic miR-181 s in GC cells. Furthermore, MEG3 could up-regulated Bcl-2 via its competing endogenous RNA (ceRNA) activity on miR-181a.

          Conclusions

          These findings suggest that lncRNA MEG3, a ceRNA of miR-181 s, could regulate gastric carcinogenesis and may serve as a potential target for antineoplastic therapies.

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          Most cited references22

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          A coding-independent function of gene and pseudogene mRNAs regulates tumour biology

          The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs possess a biological role in cancer cells that relies upon their ability to compete for microRNA binding and is independent of their protein-coding function. As a paradigm for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene (PTENP1) and the critical consequences of this interaction. We find that PTENP1 is biologically active as determined by its ability to regulate cellular levels of PTEN, and that it can exert a growth-suppressive role. We also show that PTENP1 locus is selectively lost in human cancer. We extend our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic KRAS. Further, we demonstrate that the transcripts of protein coding genes such as PTEN are also biologically active. Together, these findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs.
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            Long non-coding RNA H19 increases bladder cancer metastasis by associating with EZH2 and inhibiting E-cadherin expression.

            lncRNA H19 is essential for human tumor growth. However, little is known about whether H19 regulates bladder cancer metastasis. Here we found that H19 levels are remarkably increased in bladder cancer tissues, and upregulated H19 promotes bladder cancer cell migration in vitro and in vivo. H19 is associated with enhancer of zeste homolog 2 (EZH2), and that this association results in Wnt/β-catenin activation and subsequent downregulation of E-cadherin. A significant negative correlation is also observed between H19 levels and E-cad levels in vivo. These data suggest that upregulated H19 enhances bladder cancer metastasis by associating with EZH2 and inhibiting E-cad expression. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
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              Recent patterns in gastric cancer: a global overview.

              Until the mid-1990s, gastric cancer has been the first cause of cancer death worldwide, although rates had been declining for several decades and gastric cancer has become a relatively rare cancer in North America and in most Northern and Western Europe, but not in Eastern Europe, Russia and selected areas of Central and South America or East Asia. We analyzed gastric cancer mortality in Europe and other areas of the world from 1980 to 2005 using joinpoint regression analysis, and provided updated site-specific incidence rates from 51 selected registries. Over the last decade, the annual percent change (APC) in mortality rate was around -3, -4% for the major European countries. The APC were similar for the Republic of Korea (APC = -4.3%), Australia (-3.7%), the USA (-3.6%), Japan (-3.5%), Ukraine (-3%) and the Russian Federation (-2.8%). In Latin America, the decline was less marked, but constant with APC around -1.6% in Chile and Brazil, -2.3% in Argentina and Mexico and -2.6% in Colombia. Cancers in the fundus and pylorus are more common in high incidence and mortality areas and have been declining more than cardia gastric cancer. Steady downward trends persist in gastric cancer mortality worldwide even in middle aged population, and hence further appreciable declines are likely in the near future.
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                Author and article information

                Contributors
                wo_wfang@hotmail.com
                j-yu@ibms.pumc.edu.cn
                maren517@sohu.com
                Journal
                J Exp Clin Cancer Res
                J. Exp. Clin. Cancer Res
                Journal of Experimental & Clinical Cancer Research : CR
                BioMed Central (London )
                0392-9078
                1756-9966
                8 August 2015
                8 August 2015
                2015
                : 34
                : 1
                : 79
                Affiliations
                [ ]Department of General Surgery, China-Japan Friendship Hospital, Beijing, 100029 China
                [ ]Department of Obstetrics and gynecology, China-Japan Friendship Hospital, Beijing, 100029 China
                [ ]Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, 100005 China
                Article
                197
                10.1186/s13046-015-0197-7
                4529701
                26253106
                68146e83-e73d-45b8-8951-e2aff608a2c1
                © Peng et al. 2015

                Open Access This 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
                : 2 April 2015
                : 29 July 2015
                Categories
                Research
                Custom metadata
                © The Author(s) 2015

                Oncology & Radiotherapy
                meg3,gastric cancer,competing endogenous rna,mir-181a
                Oncology & Radiotherapy
                meg3, gastric cancer, competing endogenous rna, mir-181a

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