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      The influence of LncRNA H19 polymorphic variants on susceptibility to cancer: A systematic review and updated meta-analysis of 28 case-control studies

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          Abstract

          Objective

          Although myriad researches upon the associations between LncRNA H19 polymorphic variants (rs2839698 G>A, rs217727 G>A, rs2107425 C>T, rs2735971 A>G and rs3024270 C>G) and the susceptibility to cancer have been conducted, these results remained contradictory and perplexing. Basing on that, a systematic review and updated meta-analysis was performed to anticipate a fairly precise assessment about such associations.

          Methods

          We retrieved the electronic databases EMBASE, PubMed and Web of Science for valuable academic studies before February 28, 2021. Ultimately, 28 of which were encompassed after screening in this meta-analysis, and the available data was extracted and integrated. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) was used to evaluate such associations. For multi-level investigation, subgroup analysis derived from source of controls together with genotypic method was preformed.

          Results

          Eventually, 28 articles altogether embodying 57 studies were included in this meta-analysis. The results illuminated that LncRNA H19 polymorphisms mentioned above were all irrelevant to cancer susceptibility. Nevertheless, crucial results were found concentrated in population-based control group when subgroup analysis by source of controls were performed in H19 mutation rs2839698 and rs2735971. Meanwhile, in the stratification analysis by genotypic method, apparent cancer risks were discovered by TaqMan method in H19 mutation rs2107425 and rs3024270. Then, trial sequential analysis demonstrated that the results about such associations were firm evidence of effect.

          Conclusion

          Therefore, this meta-analysis indicated that LncRNA H19 polymorphisms were not associated with the susceptibility to human cancer. However, after the stratification analysis, inconsistent results still existed in different genotypic method and source of control. Thus, more high-quality studies on cancer patients of different factors were needed to confirm these findings.

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          Most cited references62

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          Cancer statistics, 2019

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2015, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2016, were collected by the National Center for Health Statistics. In 2019, 1,762,450 new cancer cases and 606,880 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2006-2015) was stable in women and declined by approximately 2% per year in men, whereas the cancer death rate (2007-2016) declined annually by 1.4% and 1.8%, respectively. The overall cancer death rate dropped continuously from 1991 to 2016 by a total of 27%, translating into approximately 2,629,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the racial gap in cancer mortality is slowly narrowing, socioeconomic inequalities are widening, with the most notable gaps for the most preventable cancers. For example, compared with the most affluent counties, mortality rates in the poorest counties were 2-fold higher for cervical cancer and 40% higher for male lung and liver cancers during 2012-2016. Some states are home to both the wealthiest and the poorest counties, suggesting the opportunity for more equitable dissemination of effective cancer prevention, early detection, and treatment strategies. A broader application of existing cancer control knowledge with an emphasis on disadvantaged groups would undoubtedly accelerate progress against cancer.
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            Molecular mechanisms of long noncoding RNAs.

            Long noncoding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. Here we discuss the emerging archetypes of molecular functions that lncRNAs execute-as signals, decoys, guides, and scaffolds. For each archetype, examples from several disparate biological contexts illustrate the commonality of the molecular mechanisms, and these mechanistic views provide useful explanations and predictions of biological outcomes. These archetypes of lncRNA function may be a useful framework to consider how lncRNAs acquire properties as biological signal transducers and hint at their possible origins in evolution. As new lncRNAs are being discovered at a rapid pace, the molecular mechanisms of lncRNAs are likely to be enriched and diversified. Copyright © 2011 Elsevier Inc. All rights reserved.
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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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                Author and article information

                Contributors
                Role: Data curationRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysis
                Role: Formal analysis
                Role: Formal analysis
                Role: Data curation
                Role: Writing – original draftRole: Writing – review & editing
                Role: Project administration
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                26 July 2021
                2021
                : 16
                : 7
                : e0254943
                Affiliations
                [1 ] Department of Urology, The First People’s Hospital of Lianyungang, Lianyungang Clinical Medical College of Nanjing Medical University, Lianyungang, China
                [2 ] First Clinical Medical College of Nanjing Medical University, Nanjing, China
                [3 ] Department of Surgical Oncology, Xuzhou Central Hospital, Southeast University Cancer Institute, Xuzhou, China
                Shanghai Jiao Tong University, CHINA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-3344-1262
                Article
                PONE-D-21-10970
                10.1371/journal.pone.0254943
                8312943
                34310645
                1db1d503-31fb-4cce-9955-7ced62cabd55
                © 2021 Wang 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
                : 5 April 2021
                : 6 July 2021
                Page count
                Figures: 9, Tables: 2, Pages: 18
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                People and Places
                Geographical Locations
                Asia
                China
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Metaanalysis
                Physical Sciences
                Mathematics
                Statistics
                Statistical Methods
                Metaanalysis
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Colorectal Cancer
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Carcinoma
                Hepatocellular Carcinoma
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Gastrointestinal Tumors
                Hepatocellular Carcinoma
                Medicine and Health Sciences
                Gastroenterology and Hepatology
                Liver Diseases
                Hepatocellular Carcinoma
                Biology and life sciences
                Biochemistry
                Nucleic acids
                RNA
                Non-coding RNA
                Long non-coding RNA
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Breast Tumors
                Breast Cancer
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Gastrointestinal Tumors
                Gastric Cancer
                Custom metadata
                All relevant data are within the manuscript and its Supporting Information files.

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