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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Mohammed Alshalalfa, Gary D Bader, Tarek A Bismar, Reda Alhajj
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/efb163b29cb743cc9806bfa60b30506c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:efb163b29cb743cc9806bfa60b30506c
record_format	dspace
spelling	oai:doaj.org-article:efb163b29cb743cc9806bfa60b30506c2021-11-18T08:39:22ZCoordinate microRNA-mediated regulation of protein complexes in prostate cancer.1932-620310.1371/journal.pone.0084261https://doaj.org/article/efb163b29cb743cc9806bfa60b30506c2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24391925/?tool=EBIhttps://doaj.org/toc/1932-6203MicroRNAs 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.Mohammed AlshalalfaGary D BaderTarek A BismarReda AlhajjPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e84261 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mohammed Alshalalfa Gary D Bader Tarek A Bismar Reda Alhajj Coordinate microRNA-mediated regulation of protein complexes in prostate cancer.
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.
format	article
author	Mohammed Alshalalfa Gary D Bader Tarek A Bismar Reda Alhajj
author_facet	Mohammed Alshalalfa Gary D Bader Tarek A Bismar Reda Alhajj
author_sort	Mohammed Alshalalfa
title	Coordinate microRNA-mediated regulation of protein complexes in prostate cancer.
title_short	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_sort	coordinate microrna-mediated regulation of protein complexes in prostate cancer.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/efb163b29cb743cc9806bfa60b30506c
work_keys_str_mv	AT mohammedalshalalfa coordinatemicrornamediatedregulationofproteincomplexesinprostatecancer AT garydbader coordinatemicrornamediatedregulationofproteincomplexesinprostatecancer AT tarekabismar coordinatemicrornamediatedregulationofproteincomplexesinprostatecancer AT redaalhajj coordinatemicrornamediatedregulationofproteincomplexesinprostatecancer
_version_	1718421536072794112

Coordinate microRNA-mediated regulation of protein complexes in prostate cancer.

Ejemplares similares