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      Prognostic and clinicopathological significance of long noncoding RNA H19 overexpression in human solid tumors: evidence from a meta-analysis

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          Abstract

          Background

          Many studies have reported that the expression level of lncRNA H19 was increased in various tumors. LncRNA H19 may play a significant role in cancer occurrence and development. An increased level of H19 was also associated with poor clinical outcomes of cancer patients.

          Results

          12 eligible studies were screened, with a total of 1437 cancer patients. From the results of meta-analysis, as for prognosis, the patients with high expression of lncRNA H19 were shorter in OS (HR=1.08, 95% CI: 1.05-1.12). Statistical significance was also showed in subgroup meta-analysis stratified by the cancer type, analysis type and sample size. In addition, the patients detected with high H19 expression may be poorer in DFS (HR=1.27; 95% CI = 0.97-1.56). As for clinicopathology, it showed that increased H19 was related to poor histological grades (OR=2.31, 95% CI: 1.12-4.75), positive lymph node metastasis (OR=2.29, 95 % CI: 1.21-4.34) and advanced clinical stage (OR=4.83, 95% CI: 3.16-7.39).

          Materials and Methods

          Eligible studies were collected by retrieving keywords in PubMed, Web of Science, Embase, CNKI and Wanfang database, from 1966 to April 23, 2016. This quantitative meta-analysis was performed with Stata SE12.0 and RevMan5.3 software. It aimed to explore the association between H19 expression level and prognosis and clinicopathology.

          Conclusions

          LncRNA-H19 may be a novel molecular marker for predicting solid tumors. It can also be a predictive factor of clinicopathological features in various cancers. Further studies are needed to verify the clinical utility of H19 in human cancers.

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          Most cited references33

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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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            The H19 Long non-coding RNA in cancer initiation, progression and metastasis – a proposed unifying theory

            The imprinted oncofetal long non-coding RNA (lncRNA) H19 is expressed in the embryo, down-regulated at birth and then reappears in tumors. Its role in tumor initiation and progression has long been a subject of controversy, although accumulating data suggest that H19 is one of the major genes in cancer. It is actively involved in all stages of tumorigenesis and is expressed in almost every human cancer. In this review we delineate the various functions of H19 during the different stages in the complex process of tumor progression. H19 up-regulation allows cells to enter a “selfish” survival mode in response to stress conditions, such as destabilization of the genome and hypoxia, by accelerating their proliferation rate and increasing overall cellular resistance to stress. This response is tightly correlated with nullification, dysfunction or significant down-regulation of the master tumor suppressor gene P53. The growing evidence of H19’s involvement in both proliferation and differentiation processes, together with its involvement in epithelial to mesenchymal transition (EMT) and also mesenchymal to epithelial transition (MET), has led us to conclude that some of the recent disputes and discrepancies arising from current research findings can be resolved from a viewpoint supporting the oncogenic properties of H19. According to a holistic approach, the versatile, seemingly contradictory functions of H19 are essential to, and differentially harnessed by, the tumor cell depending on its context within the process of tumor progression.
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              The imprinted H19 noncoding RNA is a primary microRNA precursor.

              Although H19 was the first imprinted noncoding transcript to be identified, the function of this conserved RNA has remained unclear. Here, we identify a 23-nucleotide microRNA derived from H19 that is endogenously expressed in human keratinocytes and neonatal mice and overexpressed in cells transfected with human or mouse H19 expression plasmids. These data demonstrate that H19 can function as a primary microRNA precursor and suggest that H19 expression results in the post-transcriptional downregulation of specific mRNAs during vertebrate development.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                13 December 2016
                4 November 2016
                : 7
                : 50
                : 83177-83186
                Affiliations
                1 Department of General Surgery, the Second Affiliated Hospital of Nanchang University, Nanchang 330000, Jiangxi Province, P. R. China
                Author notes
                Correspondence to: Zheng-ming Zhu, zzm8654@ 123456163.com
                Article
                13076
                10.18632/oncotarget.13076
                5347760
                27825121
                95f7edb0-45ea-42f9-9350-d37b6ef1eb36
                Copyright: © 2016 Liu et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 29 April 2016
                : 17 October 2016
                Categories
                Research Paper

                Oncology & Radiotherapy
                long noncoding rna,h19,carcinoma,prognosis,meta-analysis
                Oncology & Radiotherapy
                long noncoding rna, h19, carcinoma, prognosis, meta-analysis

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