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      Association between MIR499A rs3746444 polymorphism and breast cancer susceptibility: a meta-analysis

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          Abstract

          Numerous studies have investigated the association of MIR499A rs3746444 polymorphism with breast cancer susceptibility, but the results have been inconsistent. In this work, we performed a meta-analysis to obtain a more reliable estimate of the association between the polymorphism and susceptibility to breast cancer. A comprehensive literature search was conducted on PubMed, Scopus, Web of Science (WoS), China National Knowledge Infrastructure (CNKI), VIP and Wanfang databases up to January 2020. A total of 14 studies involving 6,797 cases and 8,534 controls were included for analysis under five genetic models: homozygous (GG vs. AA), heterozygous (AG vs. AA), dominant (AG + GG vs. AA), recessive (GG vs. AA + AG) and allele (G vs. A). A statistically significant association was observed between the polymorphism and an increased breast cancer susceptibility under all genetic models (homozygous, OR = 1.33, 95% CI = 1.03–1.71, P = 0.03; heterozygous, OR = 1.08, 95% CI = 1.00–1.16, P = 0.04; dominant, OR = 1.15, 95% CI = 1.02–1.30; P = 0.03; recessive, OR = 1.35, 95% CI = 1.06–1.72, P = 0.01; allele, OR = 1.12, 95% CI = 1.00–1.26, P = 0.04). Subgroup analysis based on ethnicity suggested that significant association was present only among Asians, but not Caucasians. In conclusion, MIR499A rs3746444 polymorphism was significantly associated with breast cancer susceptibility among Asians, suggesting its potential use as a genetic risk marker in this population.

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          Common genetic variants in pre-microRNAs were associated with increased risk of breast cancer in Chinese women.

          Small, noncoding RNA molecules, called microRNAs (miRNAs), are thought to function as either tumor suppressors or oncogenes. Common single-nucleotide polymorphisms (SNPs) in miRNAs may change their property through altering miRNA expression and/or maturation, and thus they may have an effect on thousands of target mRNAs, resulting in diverse functional consequences. However, it remains largely unknown whether miRNA SNPs may alter cancer susceptibility. We evaluated the associations of selected four SNPs (rs2910164, rs2292832, rs11614913, and rs3746444) in pre-miRNAs (hsa-mir-146a, hsa-mir-149, hsa-mir-196a2, and hsa-mir-499) with breast cancer risk in a case-control study of 1,009 breast cancer cases and 1,093 cancer-free controls in a population of Chinese women and we found that hsa-mir-196a2 rs11614913:T>C and hsa-mir-499 rs3746444:A>G variant genotypes were associated with significantly increased risks of breast cancer (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.02-1.48 for rs11614913:T>C; and OR, 1.25; 95% CI, 1.02-1.51 for rs3746444:A>G in a dominant genetic model) in a dose-effect manner (P for trend was 0.010 and 0.037, respectively). These findings suggest, for the first time, that common SNPs in miRNAs may contribute to breast cancer susceptibility. Further functional characterization of miRNA SNPs and their influences on target mRNAs may provide underlying mechanisms for the observed associations and disease etiology. Copyright 2008 Wiley-Liss, Inc.
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            Meta-Analysis of Genetic Association Studies

            The object of this review is to help readers to understand meta-analysis of genetic association study. Genetic association studies are a powerful approach to identify susceptibility genes for common diseases. However, the results of these studies are not consistently reproducible. In order to overcome the limitations of individual studies, larger sample sizes or meta-analysis is required. Meta-analysis is a statistical tool for combining results of different studies on the same topic, thus increasing statistical strength and precision. Meta-analysis of genetic association studies combines the results from independent studies, explores the sources of heterogeneity, and identifies subgroups associated with the factor of interest. Meta-analysis of genetic association studies is an effective tool for garnering a greater understanding of complex diseases and potentially provides new insights into gene-disease associations.
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              MicroRNA-499-5p promotes cellular invasion and tumor metastasis in colorectal cancer by targeting FOXO4 and PDCD4.

              MicroRNAs (miRNAs) regulate tumor progression and invasion via direct interaction with target messenger RNAs (mRNAs). We defined miRNAs involved in cancer metastasis (metastamirs) using an established in vitro colorectal cancer (CRC) model of minimally metastatic cells (SW480 line) from a colon adenocarcinoma primary lesion and highly metastatic cells (SW620 line) from a metastatic lymph node from the same patient 1 year later. We used microarray analysis to identify miRNAs differentially expressed in SW480 and SW620 cells, focusing on miR-499-5p as a novel candidate prometastatic miRNA whose functions in cancer had not been studied. We confirmed increased miR-499-5p levels in highly invasive CRC cell lines and lymph node-positive CRC specimens. Furthermore, enhancing the expression of miR-499-5p promoted CRC cell migration and invasion in vitro and lung and liver metastasis in vivo, while silencing its expression resulted in reduced migration and invasion. Additionally, we identified FOXO4 and PDCD4 as direct and functional targets of miR-499-5p. Collectively, these findings suggested that miR-499-5p promoted metastasis of CRC cells and may be useful as a new potential therapeutic target for CRC.
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                Author and article information

                Contributors
                sctan@ukm.edu.my
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                26 February 2020
                26 February 2020
                2020
                : 10
                : 3508
                Affiliations
                [1 ]ISNI 0000 0004 1937 1557, GRID grid.412113.4, UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, ; Kuala Lumpur, Malaysia
                [2 ]ISNI 0000 0001 2231 800X, GRID grid.11142.37, Department of Community Health, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, ; Selangor, Malaysia
                [3 ]ISNI 0000 0001 2308 5949, GRID grid.10347.31, Department of Language and Literacy Education, Faculty of Education, University of Malaya, ; Kuala Lumpur, Malaysia
                Article
                60442
                10.1038/s41598-020-60442-3
                7044335
                32103099
                0f7453f5-dfd0-4daa-a08a-5de4b515c3e6
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 6 October 2019
                : 13 February 2020
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                © The Author(s) 2020

                Uncategorized
                genetic association study,genetic markers,cancer,epidemiology,genetics research
                Uncategorized
                genetic association study, genetic markers, cancer, epidemiology, genetics research

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