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      Association between lncRNA GAS5, MEG3, and PCAT-1 Polymorphisms and Cancer Risk: A Meta-Analysis

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          Abstract

          Purpose

          Long noncoding RNAs (lncRNAs) have been widely studied, and single nucleotide polymorphisms (SNPs) in lncRNAs are considered to be genetic factors that influence cancer susceptibility. The lncRNA GAS5, MEG3, and PCAT-1 polymorphisms are shown to be possibly associated with cancer risk. The aim of this meta-analysis was to systematically evaluate this association.

          Methods

          Studies were selected from PubMed, Web of Science, Embase, Google Scholar, Cochrane Library, the Chinese National Knowledge Infrastructure (CNKI), and the Chinese Biomedical Literature Database (CBM) through inclusion and exclusion criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the random-effects model or fixed-effects model to assess the association between lncRNA polymorphisms and cancer susceptibility. Metaregression and publication bias analyses were also conducted. All analyses were performed using the Stata 12.0 software.

          Results

          Sixteen articles (covering 13750 cases and 17194 controls) were included in this meta-analysis. A significant association between SNP rs145204276 and gastric cancer risk was observed ( del vs. ins: OR = 0.79, 95%CI = 0.72‐0.86; del/del vs. ins/ins+del/ins: OR = 0.74, 95%CI = 0.59‐0.91; del/ins vs. ins/ins: OR = 0.84, 95%CI = 0.67‐1.05). For rs16901904, a decreased cancer risk was observed in three genetic models ( C vs. T: OR = 0.79, 95%CI = 0.70‐0.90; CC vs. CT+TT: OR = 0.49, 95%CI = 0.37‐0.65; CC vs. TT: OR = 0.49, 95%CI = 0.37‐0.66). No statistical significance was found in the metaregression analysis. For all of the included SNPs, no publication bias was found in all genotype models.

          Conclusions

          The rs145204276 SNP in lncRNA GAS5 is likely to be associated with gastric cancer risk, whereas the rs16901904 SNP in lncRNA PCAT-1 bears association with a decreased cancer risk.

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          Most cited references32

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          Technological Developments in lncRNA Biology.

          It is estimated that more than 90% of the mammalian genome is transcribed as non-coding RNAs. Recent evidences have established that these non-coding transcripts are not junk or just transcriptional noise, but they do serve important biological purpose. One of the rapidly expanding fields of this class of transcripts is the regulatory lncRNAs, which had been a major challenge in terms of their molecular functions and mechanisms of action. The emergence of high-throughput technologies and the development in various conventional approaches have led to the expansion of the lncRNA world. The combination of multidisciplinary approaches has proven to be essential to unravel the complexity of their regulatory networks and helped establish the importance of their existence. Here, we review the current methodologies available for discovering and investigating functions of long non-coding RNAs (lncRNAs) and focus on the powerful technological advancement available to specifically address their functional importance.
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            lncRNA GAS5 enhances G1 cell cycle arrest via binding to YBX1 to regulate p21 expression in stomach cancer

            Long non-coding RNAs (lncRNAs), which have evolved as important gene expression modulators, are involved in human malignancies. The down-regulation of lncRNA growth arrest specific transcript 5 (GAS5) has been reported in several cancers, however, the underlying mechanism of lncRNA GAS5 in stomach cancer is poorly understood. In this study, we found that lncRNA GAS5 had lower expression in stomach cancer tissues than the normal counterparts. lncRNA GAS5 was shown to interact with Y-box binding protein 1 (YBX1), and lncRNA GAS5 knockdown was shown to accelerate YBX1 protein turnover without affecting YBX1 transcription. lncRNA GAS5 down-regulation reduced the YBX1 protein level, which decreased YBX1-transactivated p21 expression and abolished G1 phase cell cycle arrest in stomach cancer. These results delineate a novel mechanism of lncRNA GAS5 in suppressing stomach carcinogenesis, and the lncRNA GAS5/YBX1/p21 pathway we discovered may provide useful targets for developing lncRNA-based therapies for stomach cancer.
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              Long noncoding RNA in liver diseases.

              The identification of the presence of large RNA transcripts that do not code for proteins but that may have biological functions has provided an important new perspective in gene regulation. These long noncoding RNAs (lncRNAs) are being increasingly recognized to contribute to many biological processes through diverse mechanisms. The roles of these emerging genes are being recognized across kingdoms. These findings are profoundly altering our understanding of disease pathobiology and leading to the emergence of new biological concepts underlying human diseases. Strategies for the discovery and characterization of lncRNAs are highlighted. Several lncRNAs have been described in liver disease, and in liver cancers in particular. Their molecular mechanisms of action, function, and contributions to disease pathophysiology are reviewed. LncRNA genes associated with liver diseases have potential roles as biomarkers of disease diagnosis, prognosis, or therapeutic response as well as direct targets for therapeutic intervention. The emerging knowledge in this rapidly advancing field offers promise for new fundamental knowledge and clinical applications that will be relevant for human liver diseases. © 2014 by the American Association for the Study of Liver Diseases.
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                Author and article information

                Contributors
                Journal
                Dis Markers
                Dis. Markers
                DM
                Disease Markers
                Hindawi
                0278-0240
                1875-8630
                2020
                28 March 2020
                : 2020
                : 6723487
                Affiliations
                1Department of Pharmacy and Medicine Pharmacy, Jiang Su College of Nursing, Huian, 223003, China
                2Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China
                3Zhejiang Provincial Key Lab of Geriatrics, Department of Geriatrics, Zhejiang Hospital, Hangzhou 310013, China
                Author notes

                Guest Editor: Ioannis Kosmas

                Author information
                https://orcid.org/0000-0001-7610-3119
                https://orcid.org/0000-0002-5883-3094
                https://orcid.org/0000-0002-7759-0219
                https://orcid.org/0000-0002-3205-2222
                https://orcid.org/0000-0001-9559-2640
                https://orcid.org/0000-0001-7061-4479
                https://orcid.org/0000-0003-3980-2011
                Article
                10.1155/2020/6723487
                7142337
                c66176d9-5f7b-4aec-9ae3-0925c4231426
                Copyright © 2020 Xiaoyan Dong et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 June 2019
                : 15 October 2019
                : 28 November 2019
                Funding
                Funded by: Technology Projects of Zhejiang Province
                Award ID: 2017ZB002
                Funded by: Health Bureau of Zhejiang Province
                Award ID: 2017KY189
                Award ID: 2017KY188
                Award ID: 2019RC093
                Award ID: 2019KY263
                Award ID: 2019RC091
                Award ID: 2019KY257
                Award ID: 2015KYA001
                Award ID: 2015DTA001
                Award ID: WKJ2011-2-014
                Funded by: Natural Science Foundation of Zhejiang Province
                Award ID: LQ16H020006
                Award ID: LY16H20002
                Funded by: Science and Technology Department of Zhejiang Province
                Award ID: 2016C34002
                Funded by: National Natural Science Foundation of China
                Award ID: 31702144
                Award ID: 31700307
                Award ID: 31201040
                Award ID: 81771520
                Categories
                Research Article

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