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      miR-499 rs3746444 and miR-196a-2 rs11614913 Are Associated with the Risk of Glioma, but Not the Prognosis

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          Abstract

          Previous studies of correlations of microRNA (miR)-499 rs3746444 and miR-196a-2 rs11614913 polymorphisms with glioma risk have yielded inconsistent results. In this study, relationships between these two polymorphisms and glioma risk and survival were evaluated. In total, 605 patients and 1,300 controls were genotyped. rs3746444 increased glioma risk in five genetic models (GA versus AA, odds ratio [OR], 95% confidence interval [CI] = 1.31 [1.05–1.66], p = 0.02; GG versus AA, OR [95% CI] = 10.70 [6.13–18.69], p < 0.0001; GA + GG versus AA, OR [95% CI] = 1.82 [1.47–2.24], p < 0.0001; GG versus AA + GA, OR [95% CI] = 9.99 [5.74–17.40], p < 0.0001; G versus A, OR [95% CI] = 2.18 [1.82–2.60], p < 0.0001). rs11614913 decreased glioma risk in a recessive model (OR [95% CI] = 0.79 [0.64–0.97], p = 0.03). No relationships between either SNP and survival were found. rs3746444 in the miR-499 seed region could affect target recognition. Bioinformatics analyses indicated that miR-499 rs3746444 is involved in various biological processes and pathways, including “cell adhesion molecule binding,” “positive regulation of catabolic process,” “NF-kappa B pathway,” and “PI3K-Akt pathway,” by targeting mRNAs. Our results suggested that miR-499 rs3746444 and miR-196a-2 rs11614913 have crucial roles in glioma susceptibility.

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          Abstract

          Relationships between miR-499 rs3746444 and miR-196a-2 rs11614913 polymorphisms and glioma susceptibility and survival were investigated. rs3746444 increased glioma risk, whereas rs11614913 decreased glioma risk. However, no relationships between either SNP and survival were found. These results first highlight that miR-499 rs3746444 and miR-196a-2 rs11614913 have crucial roles in glioma susceptibility.

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          Most cited references35

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          Genetic variation in microRNA networks: the implications for cancer research.

          Many studies have highlighted the role that microRNAs have in physiological processes and how their deregulation can lead to cancer. More recently, it has been proposed that the presence of single nucleotide polymorphisms in microRNA genes, their processing machinery and target binding sites affects cancer risk, treatment efficacy and patient prognosis. In reviewing this new field of cancer biology, we describe the methodological approaches of these studies and make recommendations for which strategies will be most informative in the future.
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            The European Association for Neuro-Oncology guideline provides recommendations for the clinical care of adult patients with astrocytic and oligodendroglial gliomas, including glioblastomas. The guideline is based on the 2016 WHO classification of tumours of the central nervous system and on scientific developments since the 2014 guideline. The recommendations focus on pathological and radiological diagnostics, and the main treatment modalities of surgery, radiotherapy, and pharmacotherapy. In this guideline we have also integrated the results from contemporary clinical trials that have changed clinical practice. The guideline aims to provide guidance for diagnostic and management decisions, while limiting unnecessary treatments and costs. The recommendations are a resource for professionals involved in the management of patients with glioma, for patients and caregivers, and for health-care providers in Europe. The implementation of this guideline requires multidisciplinary structures of care, and defined processes of diagnosis and treatment.
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              High-throughput oncogene mutation profiling in human cancer.

              Systematic efforts are underway to decipher the genetic changes associated with tumor initiation and progression. However, widespread clinical application of this information is hampered by an inability to identify critical genetic events across the spectrum of human tumors with adequate sensitivity and scalability. Here, we have adapted high-throughput genotyping to query 238 known oncogene mutations across 1,000 human tumor samples. This approach established robust mutation distributions spanning 17 cancer types. Of 17 oncogenes analyzed, we found 14 to be mutated at least once, and 298 (30%) samples carried at least one mutation. Moreover, we identified previously unrecognized oncogene mutations in several tumor types and observed an unexpectedly high number of co-occurring mutations. These results offer a new dimension in tumor genetics, where mutations involving multiple cancer genes may be interrogated simultaneously and in 'real time' to guide cancer classification and rational therapeutic intervention.
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                Author and article information

                Contributors
                Journal
                Mol Ther Nucleic Acids
                Molecular Therapy. Nucleic Acids
                American Society of Gene & Cell Therapy
                2162-2531
                02 September 2020
                04 December 2020
                02 September 2020
                : 22
                : 340-351
                Affiliations
                [1 ]Department of Breast Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
                [2 ]Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
                [3 ]Department of Neurosurgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
                [4 ]Department of Neurology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
                Author notes
                []Corresponding author Zhijun Dai, Department of Breast Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China. dzj0911@ 123456126.com
                [5]

                These authors contributed equally to this work.

                Article
                S2162-2531(20)30268-7
                10.1016/j.omtn.2020.08.038
                7527625
                b47687f0-f70f-478c-8045-cf9189ae0002
                © 2020 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 19 January 2020
                : 28 August 2020
                Categories
                Original Article

                Molecular medicine
                glioma,mir-499,mir-196a-2,single nucleotide polymorphism,susceptibility,survival
                Molecular medicine
                glioma, mir-499, mir-196a-2, single nucleotide polymorphism, susceptibility, survival

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