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      Identification and Analysis of Human Sex-biased MicroRNAs

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          Abstract

          Sex differences are widely observed under various circumstances ranging from physiological processes to therapeutic responses, and a myriad of sex-biased genes have been identified. In recent years, transcriptomic datasets of microRNAs (miRNAs), an important class of non-coding RNAs, become increasingly accessible. However, comprehensive analysis of sex difference in miRNA expression has not been performed. Here, we identified the differentially-expressed miRNAs between males and females by examining the transcriptomic datasets available in public databases and conducted a systemic analysis of their biological characteristics. Consequently, we identified 73 female-biased miRNAs (FmiRs) and 163 male-biased miRNAs (MmiRs) across four tissues including brain, colorectal mucosa, peripheral blood, and cord blood. Our results suggest that compared to FmiRs, MmiRs tend to be clustered in the human genome and exhibit higher evolutionary rate, higher expression tissue specificity, and lower disease spectrum width. In addition, functional enrichment analysis of miRNAs show that FmiR genes are significantly associated with metabolism process and cell cycle process, whereas MmiR genes tend to be enriched for functions like histone modification and circadian rhythm. In all, the identification and analysis of sex-biased miRNAs together could provide new insights into the biological differences between females and males and facilitate the exploration of sex-biased disease susceptibility and therapy.

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          Most cited references37

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          Roles for microRNAs in conferring robustness to biological processes.

          Biological systems use a variety of mechanisms to maintain their functions in the face of environmental and genetic perturbations. Increasing evidence suggests that, among their roles as posttranscriptional repressors of gene expression, microRNAs (miRNAs) help to confer robustness to biological processes by reinforcing transcriptional programs and attenuating aberrant transcripts, and they may in some network contexts help suppress random fluctuations in transcript copy number. These activities have important consequences for normal development and physiology, disease, and evolution. Here, we will discuss examples and principles of miRNAs that contribute to robustness in animal systems. Copyright © 2012 Elsevier Inc. All rights reserved.
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            The Gene Expression Omnibus Database.

            The Gene Expression Omnibus (GEO) database is an international public repository that archives and freely distributes high-throughput gene expression and other functional genomics data sets. Created in 2000 as a worldwide resource for gene expression studies, GEO has evolved with rapidly changing technologies and now accepts high-throughput data for many other data applications, including those that examine genome methylation, chromatin structure, and genome-protein interactions. GEO supports community-derived reporting standards that specify provision of several critical study elements including raw data, processed data, and descriptive metadata. The database not only provides access to data for tens of thousands of studies, but also offers various Web-based tools and strategies that enable users to locate data relevant to their specific interests, as well as to visualize and analyze the data. This chapter includes detailed descriptions of methods to query and download GEO data and use the analysis and visualization tools. The GEO homepage is at http://www.ncbi.nlm.nih.gov/geo/.
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              Characterization of microRNA expression profiles in normal human tissues

              Background Measuring the quantity of miRNAs in tissues of different physiological and pathological conditions is an important first step to investigate the functions of miRNAs. Matched samples from normal state can provide essential baseline references to analyze the variation of miRNA abundance. Results We provided expression data of 345 miRNAs in 40 normal human tissues, which identified universally expressed miRNAs, and several groups of miRNAs expressed exclusively or preferentially in certain tissue types. Many miRNAs with co-regulated expression patterns are located within the same genomic clusters, and candidate transcriptional factors that control the pattern of their expression may be identified by a comparative genomic strategy. Hierarchical clustering of normal tissues by their miRNA expression profiles basically followed the structure, anatomical locations, and physiological functions of the organs, suggesting that functions of a miRNA could be appreciated by linking to the biologies of the tissues in which it is uniquely expressed. Many predicted target genes of miRNAs that had specific reduced expression in brain and peripheral blood mononuclear cells are required for embryonic development of the nervous and hematopoietic systems based on database search. Conclusion We presented a global view of tissue distribution of miRNAs in relation to their chromosomal locations and genomic structures. We also described evidence from the cis-regulatory elements and the predicted target genes of miRNAs to support their tissue-specific functional roles to regulate the physiologies of the normal tissues in which they are expressed.
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                Author and article information

                Contributors
                Journal
                Genomics Proteomics Bioinformatics
                Genomics Proteomics Bioinformatics
                Genomics, Proteomics & Bioinformatics
                Elsevier
                1672-0229
                2210-3244
                11 July 2018
                June 2018
                11 July 2018
                : 16
                : 3
                : 200-211
                Affiliations
                [1 ]Department of Biomedical Informatics, Department of Physiology and Pathophysiology, Center for Noncoding RNA Medicine, MOE Key Laboratory of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University, Beijing 100191, China
                [2 ]Department of Physiology and Pathophysiology, Center for Noncoding RNA Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China
                [3 ]Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
                Author notes
                [#]

                Equal contribution.

                [a]

                ORCID: 0000-0001-6223-5225.

                [b]

                ORCID: 0000-0003-3646-7772.

                [c]

                ORCID: 0000-0001-9934-4556.

                [d]

                ORCID: 0000-0001-5221-8026.

                [e]

                ORCID: 0000-0001-8150-2923.

                [f]

                ORCID: 0000-0003-3018-5221.

                [g]

                ORCID: 0000-0001-5685-066X.

                Article
                S1672-0229(18)30130-X
                10.1016/j.gpb.2018.03.004
                6076379
                30005964
                76f408ba-2938-4ca3-bf60-f537cb574d10
                © 2018 The Authors

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

                History
                : 2 November 2017
                : 9 February 2018
                : 2 March 2018
                Categories
                Original Research

                sex bias,micrornas,conservation,disease association,personalized medicine

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