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      WBSMDA: Within and Between Score for MiRNA-Disease Association prediction

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          Abstract

          Increasing evidences have indicated that microRNAs (miRNAs) are functionally associated with the development and progression of various complex human diseases. However, the roles of miRNAs in multiple biological processes or various diseases and their underlying molecular mechanisms still have not been fully understood yet. Predicting potential miRNA-disease associations by integrating various heterogeneous biological datasets is of great significance to the biomedical research. Computational methods could obtain potential miRNA-disease associations in a short time, which significantly reduce the experimental time and cost. Considering the limitations in previous computational methods, we developed the model of Within and Between Score for MiRNA-Disease Association prediction (WBSMDA) to predict potential miRNAs associated with various complex diseases. WBSMDA could be applied to the diseases without any known related miRNAs. The AUC of 0.8031 based on Leave-one-out cross validation has demonstrated its reliable performance. WBSMDA was further applied to Colon Neoplasms, Prostate Neoplasms, and Lymphoma for the identification of their potential related miRNAs. As a result, 90%, 84%, and 80% of predicted miRNA-disease pairs in the top 50 prediction list for these three diseases have been confirmed by recent experimental literatures, respectively. It is anticipated that WBSMDA would be a useful resource for potential miRNA-disease association identification.

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          Most cited references35

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          Switching from repression to activation: microRNAs can up-regulate translation.

          AU-rich elements (AREs) and microRNA target sites are conserved sequences in messenger RNA (mRNA) 3' untranslated regions (3'UTRs) that control gene expression posttranscriptionally. Upon cell cycle arrest, the ARE in tumor necrosis factor-alpha (TNFalpha) mRNA is transformed into a translation activation signal, recruiting Argonaute (AGO) and fragile X mental retardation-related protein 1 (FXR1), factors associated with micro-ribonucleoproteins (microRNPs). We show that human microRNA miR369-3 directs association of these proteins with the AREs to activate translation. Furthermore, we document that two well-studied microRNAs-Let-7 and the synthetic microRNA miRcxcr4-likewise induce translation up-regulation of target mRNAs on cell cycle arrest, yet they repress translation in proliferating cells. Thus, activation is a common function of microRNPs on cell cycle arrest. We propose that translation regulation by microRNPs oscillates between repression and activation during the cell cycle.
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              Mechanisms of gene silencing by double-stranded RNA.

              Double-stranded RNA (dsRNA) is an important regulator of gene expression in many eukaryotes. It triggers different types of gene silencing that are collectively referred to as RNA silencing or RNA interference. A key step in known silencing pathways is the processing of dsRNAs into short RNA duplexes of characteristic size and structure. These short dsRNAs guide RNA silencing by specific and distinct mechanisms. Many components of the RNA silencing machinery still need to be identified and characterized, but a more complete understanding of the process is imminent.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                16 February 2016
                2016
                : 6
                : 21106
                Affiliations
                [1 ]National Center for Mathematics and Interdisciplinary Sciences, Chinese Academy of Sciences , Beijing, 100190, China
                [2 ]Academy of Mathematics and Systems Science, Chinese Academy of Sciences , Beijing, 100190, China
                [3 ]Institute of Information and Control, Hangzhou Dianzi University , Hangzhou, 310018, China
                [4 ]Department of Automation, Tsinghua University , Beijing, 100084, China
                [5 ]School of Mechanical, Electrical & Information Engineering, Shandong University , Weihai, 264209, China
                [6 ]School of Computer Science and Technology, China University of Mining and Technology , Xuzhou, 221116, China
                [7 ]Institute of Computing Technology, Chinese Academy of Sciences , Beijing, 100190, China
                [8 ]University of Chinese Academy of Sciences , Beijing, 100049, China
                [9 ]School of Economics and Management, Beihang University , Beijing, 100191, China
                [10 ]Key Lab of Intelligent Information Processing of Chinese Academy of Sciences, Institute of Computing Technology, Chinese Academy of Sciences , Beijing, 100190, China
                Author notes
                [*]

                These authors contributed equally to this work.

                Article
                srep21106
                10.1038/srep21106
                4754743
                26880032
                b5efeca4-b92c-4f63-8a4b-98de2d2adabf
                Copyright © 2016, Macmillan Publishers Limited

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 15 November 2015
                : 18 January 2016
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