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Coordinate MicroRNA-Mediated Regulation of Protein Complexes in Prostate Cancer

MicroRNAs are a class of small non-coding regulatory RNA molecules that regulate mRNAs post-transcriptionally. Recent evidence has shown that miRNAs target entire functionally related proteins such as protein complexes and biological pathways. However, characterizing the influence of miRNAs on genes...

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Autores principales: Alshalalfa, Mohammed, D. Bader, Gary, Bismar, Tarek A., Alhajj, Reda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877262/
https://www.ncbi.nlm.nih.gov/pubmed/24391925
http://dx.doi.org/10.1371/journal.pone.0084261
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author Alshalalfa, Mohammed
D. Bader, Gary
Bismar, Tarek A.
Alhajj, Reda
author_facet Alshalalfa, Mohammed
D. Bader, Gary
Bismar, Tarek A.
Alhajj, Reda
author_sort Alshalalfa, Mohammed
collection PubMed
description MicroRNAs are a class of small non-coding regulatory RNA molecules that regulate mRNAs post-transcriptionally. Recent evidence has shown that miRNAs target entire functionally related proteins such as protein complexes and biological pathways. However, characterizing the influence of miRNAs on genes whose encoded proteins are part of protein complexes has not been studied in the context of disease. We propose an entropy-based framework to identify miRNA-mediated dysregulation of functionally related proteins during prostate cancer progression. The proposed framework uses experimentally verified miRNA-target interactions, functionally related proteins and expression data to identify miRNA-influenced protein complexes in prostate cancer, and identify genes that are dysregulated as a result. The framework constructs correlation matrixes between functionally related proteins and miRNAs that have targets in the complex, and assesses the changes in the Shannon entropy of the modules across different stages of prostate cancer. Results reveal that SMAD4 and HDAC containing protein complexes are highly affected and disrupted by miRNAs, particularly miRNA-1 and miRNA-16. Using biological pathways to define functionally related proteins reveals that NF-kB-, RAS-, and Syndecan-mediated pathways are dysregulated due to miRNA-1- and miRNA-16-mediated regulation. These results suggest that miRNA-1 and miRNA-16 are important master regulators of miRNA-mediated regulation in prostate cancer. Moreover, results reveal that miRNAs with high-influence on the disrupted protein complexes are diagnostic and prognostic biomarker candidates for prostate cancer progression. The observation of miRNA-mediated protein complex regulation and miRNA-mediated pathway regulation, with partial experimental verification from previous studies, demonstrates that our framework is a promising approach for the identification of novel miRNAs and protein complexes related to disease progression.
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spelling pubmed-38772622014-01-03 Coordinate MicroRNA-Mediated Regulation of Protein Complexes in Prostate Cancer Alshalalfa, Mohammed D. Bader, Gary Bismar, Tarek A. Alhajj, Reda PLoS One Research Article MicroRNAs are a class of small non-coding regulatory RNA molecules that regulate mRNAs post-transcriptionally. Recent evidence has shown that miRNAs target entire functionally related proteins such as protein complexes and biological pathways. However, characterizing the influence of miRNAs on genes whose encoded proteins are part of protein complexes has not been studied in the context of disease. We propose an entropy-based framework to identify miRNA-mediated dysregulation of functionally related proteins during prostate cancer progression. The proposed framework uses experimentally verified miRNA-target interactions, functionally related proteins and expression data to identify miRNA-influenced protein complexes in prostate cancer, and identify genes that are dysregulated as a result. The framework constructs correlation matrixes between functionally related proteins and miRNAs that have targets in the complex, and assesses the changes in the Shannon entropy of the modules across different stages of prostate cancer. Results reveal that SMAD4 and HDAC containing protein complexes are highly affected and disrupted by miRNAs, particularly miRNA-1 and miRNA-16. Using biological pathways to define functionally related proteins reveals that NF-kB-, RAS-, and Syndecan-mediated pathways are dysregulated due to miRNA-1- and miRNA-16-mediated regulation. These results suggest that miRNA-1 and miRNA-16 are important master regulators of miRNA-mediated regulation in prostate cancer. Moreover, results reveal that miRNAs with high-influence on the disrupted protein complexes are diagnostic and prognostic biomarker candidates for prostate cancer progression. The observation of miRNA-mediated protein complex regulation and miRNA-mediated pathway regulation, with partial experimental verification from previous studies, demonstrates that our framework is a promising approach for the identification of novel miRNAs and protein complexes related to disease progression. Public Library of Science 2013-12-31 /pmc/articles/PMC3877262/ /pubmed/24391925 http://dx.doi.org/10.1371/journal.pone.0084261 Text en © 2013 Alshalalfa et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Alshalalfa, Mohammed
D. Bader, Gary
Bismar, Tarek A.
Alhajj, Reda
Coordinate MicroRNA-Mediated Regulation of Protein Complexes in Prostate Cancer
title Coordinate MicroRNA-Mediated Regulation of Protein Complexes in Prostate Cancer
title_full Coordinate MicroRNA-Mediated Regulation of Protein Complexes in Prostate Cancer
title_fullStr Coordinate MicroRNA-Mediated Regulation of Protein Complexes in Prostate Cancer
title_full_unstemmed Coordinate MicroRNA-Mediated Regulation of Protein Complexes in Prostate Cancer
title_short Coordinate MicroRNA-Mediated Regulation of Protein Complexes in Prostate Cancer
title_sort coordinate microrna-mediated regulation of protein complexes in prostate cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877262/
https://www.ncbi.nlm.nih.gov/pubmed/24391925
http://dx.doi.org/10.1371/journal.pone.0084261
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