Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Junpeng, Le, Thuc D, Liu, Lin, Li, Jiuyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
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
_version_ 1782518909336813568
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
work_keys_str_mv AT zhangjunpeng identifyingmirnaspongemodulesusingbiclusteringandregulatoryscores
AT lethucd identifyingmirnaspongemodulesusingbiclusteringandregulatoryscores
AT liulin identifyingmirnaspongemodulesusingbiclusteringandregulatoryscores
AT lijiuyong identifyingmirnaspongemodulesusingbiclusteringandregulatoryscores