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Identifying miRNA sponge modules using biclustering and regulatory scores
BACKGROUND: MicroRNA (miRNA) sponges with multiple tandem miRNA binding sequences can sequester miRNAs from their endogenous target mRNAs. Therefore, miRNA sponge acting as a decoy is extremely important for long-term loss-of-function studies both in vivo and in silico. Recently, a growing number of...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374547/ https://www.ncbi.nlm.nih.gov/pubmed/28361682 http://dx.doi.org/10.1186/s12859-017-1467-5 |
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author | Zhang, Junpeng Le, Thuc D Liu, Lin Li, Jiuyong |
author_facet | Zhang, Junpeng Le, Thuc D Liu, Lin Li, Jiuyong |
author_sort | Zhang, Junpeng |
collection | PubMed |
description | BACKGROUND: MicroRNA (miRNA) sponges with multiple tandem miRNA binding sequences can sequester miRNAs from their endogenous target mRNAs. Therefore, miRNA sponge acting as a decoy is extremely important for long-term loss-of-function studies both in vivo and in silico. Recently, a growing number of in silico methods have been used as an effective technique to generate hypotheses for in vivo methods for studying the biological functions and regulatory mechanisms of miRNA sponges. However, most existing in silico methods only focus on studying miRNA sponge interactions or networks in cancer, the module-level properties of miRNA sponges in cancer is still largely unknown. RESULTS: We propose a novel in silico method, called miRSM (miRNA Sponge Module) to infer miRNA sponge modules in breast cancer. We apply miRSM to the breast invasive carcinoma (BRCA) dataset provided by The Cancer Genome Altas (TCGA), and make functional validation of the computational results. We discover that most miRNA sponge interactions are module-conserved across two modules, and a minority of miRNA sponge interactions are module-specific, existing only in a single module. Through functional annotation and differential expression analysis, we also find that the modules discovered using miRSM are functional miRNA sponge modules associated with BRCA. Moreover, the module-specific miRNA sponge interactions among miRNA sponge modules may be involved in the progression and development of BRCA. Our experimental results show that miRSM is comparable to the benchmark methods in recovering experimentally confirmed miRNA sponge interactions, and miRSM outperforms the benchmark methods in identifying interactions that are related to breast cancer. CONCLUSIONS: Altogether, the functional validation results demonstrate that miRSM is a promising method to identify miRNA sponge modules and interactions, and may provide new insights for understanding the roles of miRNA sponges in cancer progression and development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-017-1467-5) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5374547 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-53745472017-03-31 Identifying miRNA sponge modules using biclustering and regulatory scores Zhang, Junpeng Le, Thuc D Liu, Lin Li, Jiuyong BMC Bioinformatics Research BACKGROUND: MicroRNA (miRNA) sponges with multiple tandem miRNA binding sequences can sequester miRNAs from their endogenous target mRNAs. Therefore, miRNA sponge acting as a decoy is extremely important for long-term loss-of-function studies both in vivo and in silico. Recently, a growing number of in silico methods have been used as an effective technique to generate hypotheses for in vivo methods for studying the biological functions and regulatory mechanisms of miRNA sponges. However, most existing in silico methods only focus on studying miRNA sponge interactions or networks in cancer, the module-level properties of miRNA sponges in cancer is still largely unknown. RESULTS: We propose a novel in silico method, called miRSM (miRNA Sponge Module) to infer miRNA sponge modules in breast cancer. We apply miRSM to the breast invasive carcinoma (BRCA) dataset provided by The Cancer Genome Altas (TCGA), and make functional validation of the computational results. We discover that most miRNA sponge interactions are module-conserved across two modules, and a minority of miRNA sponge interactions are module-specific, existing only in a single module. Through functional annotation and differential expression analysis, we also find that the modules discovered using miRSM are functional miRNA sponge modules associated with BRCA. Moreover, the module-specific miRNA sponge interactions among miRNA sponge modules may be involved in the progression and development of BRCA. Our experimental results show that miRSM is comparable to the benchmark methods in recovering experimentally confirmed miRNA sponge interactions, and miRSM outperforms the benchmark methods in identifying interactions that are related to breast cancer. CONCLUSIONS: Altogether, the functional validation results demonstrate that miRSM is a promising method to identify miRNA sponge modules and interactions, and may provide new insights for understanding the roles of miRNA sponges in cancer progression and development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-017-1467-5) contains supplementary material, which is available to authorized users. BioMed Central 2017-03-14 /pmc/articles/PMC5374547/ /pubmed/28361682 http://dx.doi.org/10.1186/s12859-017-1467-5 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Zhang, Junpeng Le, Thuc D Liu, Lin Li, Jiuyong Identifying miRNA sponge modules using biclustering and regulatory scores |
title | Identifying miRNA sponge modules using biclustering and regulatory scores |
title_full | Identifying miRNA sponge modules using biclustering and regulatory scores |
title_fullStr | Identifying miRNA sponge modules using biclustering and regulatory scores |
title_full_unstemmed | Identifying miRNA sponge modules using biclustering and regulatory scores |
title_short | Identifying miRNA sponge modules using biclustering and regulatory scores |
title_sort | identifying mirna sponge modules using biclustering and regulatory scores |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374547/ https://www.ncbi.nlm.nih.gov/pubmed/28361682 http://dx.doi.org/10.1186/s12859-017-1467-5 |
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