Integration of miRNA and mRNA expression profiles reveals microRNA-regulated networks during muscle wasting in cardiac cachexia

Abstract Cardiac cachexia (CC) is a common complication of heart failure (HF) associated with muscle wasting and poor patient prognosis. Although different mechanisms have been proposed to explain muscle wasting during CC, its pathogenesis is still not understood. Here, we described an integrative a...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Leonardo N. Moraes, Geysson J. Fernandez, Ivan J. Vechetti-Júnior, Paula P. Freire, Rodrigo W. A. Souza, Rolando A. R. Villacis, Silvia R. Rogatto, Patricia P. Reis, Maeli Dal-Pai-Silva, Robson F. Carvalho
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2017
Materias:
R
Q
Acceso en línea:https://doaj.org/article/3aabbe15d141491ea7bb3c989e3a3e00
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:3aabbe15d141491ea7bb3c989e3a3e00
record_format dspace
spelling oai:doaj.org-article:3aabbe15d141491ea7bb3c989e3a3e002021-12-02T16:06:54ZIntegration of miRNA and mRNA expression profiles reveals microRNA-regulated networks during muscle wasting in cardiac cachexia10.1038/s41598-017-07236-22045-2322https://doaj.org/article/3aabbe15d141491ea7bb3c989e3a3e002017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07236-2https://doaj.org/toc/2045-2322Abstract Cardiac cachexia (CC) is a common complication of heart failure (HF) associated with muscle wasting and poor patient prognosis. Although different mechanisms have been proposed to explain muscle wasting during CC, its pathogenesis is still not understood. Here, we described an integrative analysis between miRNA and mRNA expression profiles of muscle wasting during CC. Global gene expression profiling identified 1,281 genes and 19 miRNAs differentially expressed in muscle wasting during CC. Several of these deregulated genes are known or putative targets of the altered miRNAs, including miR-29a-3p, miR-29b-3p, miR-210-5p, miR-214, and miR-489. Gene ontology analysis on integrative mRNA/miRNA expression profiling data revealed miRNA interactions affecting genes that regulate extra-cellular matrix (ECM) organization, proteasome protein degradation, citric acid cycle and respiratory electron transport. We further identified 11 miRNAs, including miR-29a-3p and miR-29b-3p, which target 21 transcripts encoding the collagen proteins related to ECM organization. Integrative miRNA and mRNA global expression data allowed us to identify miRNA target genes involved in skeletal muscle wasting in CC. Our functional experiments in C2C12 cells confirmed that miR-29b down-regulates collagen genes and contributes to muscle cell atrophy. Collectively, our results suggest that key ECM-associated miRNAs and their target genes may contribute to CC in HF.Leonardo N. MoraesGeysson J. FernandezIvan J. Vechetti-JúniorPaula P. FreireRodrigo W. A. SouzaRolando A. R. VillacisSilvia R. RogattoPatricia P. ReisMaeli Dal-Pai-SilvaRobson F. CarvalhoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Leonardo N. Moraes
Geysson J. Fernandez
Ivan J. Vechetti-Júnior
Paula P. Freire
Rodrigo W. A. Souza
Rolando A. R. Villacis
Silvia R. Rogatto
Patricia P. Reis
Maeli Dal-Pai-Silva
Robson F. Carvalho
Integration of miRNA and mRNA expression profiles reveals microRNA-regulated networks during muscle wasting in cardiac cachexia
description Abstract Cardiac cachexia (CC) is a common complication of heart failure (HF) associated with muscle wasting and poor patient prognosis. Although different mechanisms have been proposed to explain muscle wasting during CC, its pathogenesis is still not understood. Here, we described an integrative analysis between miRNA and mRNA expression profiles of muscle wasting during CC. Global gene expression profiling identified 1,281 genes and 19 miRNAs differentially expressed in muscle wasting during CC. Several of these deregulated genes are known or putative targets of the altered miRNAs, including miR-29a-3p, miR-29b-3p, miR-210-5p, miR-214, and miR-489. Gene ontology analysis on integrative mRNA/miRNA expression profiling data revealed miRNA interactions affecting genes that regulate extra-cellular matrix (ECM) organization, proteasome protein degradation, citric acid cycle and respiratory electron transport. We further identified 11 miRNAs, including miR-29a-3p and miR-29b-3p, which target 21 transcripts encoding the collagen proteins related to ECM organization. Integrative miRNA and mRNA global expression data allowed us to identify miRNA target genes involved in skeletal muscle wasting in CC. Our functional experiments in C2C12 cells confirmed that miR-29b down-regulates collagen genes and contributes to muscle cell atrophy. Collectively, our results suggest that key ECM-associated miRNAs and their target genes may contribute to CC in HF.
format article
author Leonardo N. Moraes
Geysson J. Fernandez
Ivan J. Vechetti-Júnior
Paula P. Freire
Rodrigo W. A. Souza
Rolando A. R. Villacis
Silvia R. Rogatto
Patricia P. Reis
Maeli Dal-Pai-Silva
Robson F. Carvalho
author_facet Leonardo N. Moraes
Geysson J. Fernandez
Ivan J. Vechetti-Júnior
Paula P. Freire
Rodrigo W. A. Souza
Rolando A. R. Villacis
Silvia R. Rogatto
Patricia P. Reis
Maeli Dal-Pai-Silva
Robson F. Carvalho
author_sort Leonardo N. Moraes
title Integration of miRNA and mRNA expression profiles reveals microRNA-regulated networks during muscle wasting in cardiac cachexia
title_short Integration of miRNA and mRNA expression profiles reveals microRNA-regulated networks during muscle wasting in cardiac cachexia
title_full Integration of miRNA and mRNA expression profiles reveals microRNA-regulated networks during muscle wasting in cardiac cachexia
title_fullStr Integration of miRNA and mRNA expression profiles reveals microRNA-regulated networks during muscle wasting in cardiac cachexia
title_full_unstemmed Integration of miRNA and mRNA expression profiles reveals microRNA-regulated networks during muscle wasting in cardiac cachexia
title_sort integration of mirna and mrna expression profiles reveals microrna-regulated networks during muscle wasting in cardiac cachexia
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/3aabbe15d141491ea7bb3c989e3a3e00
work_keys_str_mv AT leonardonmoraes integrationofmirnaandmrnaexpressionprofilesrevealsmicrornaregulatednetworksduringmusclewastingincardiaccachexia
AT geyssonjfernandez integrationofmirnaandmrnaexpressionprofilesrevealsmicrornaregulatednetworksduringmusclewastingincardiaccachexia
AT ivanjvechettijunior integrationofmirnaandmrnaexpressionprofilesrevealsmicrornaregulatednetworksduringmusclewastingincardiaccachexia
AT paulapfreire integrationofmirnaandmrnaexpressionprofilesrevealsmicrornaregulatednetworksduringmusclewastingincardiaccachexia
AT rodrigowasouza integrationofmirnaandmrnaexpressionprofilesrevealsmicrornaregulatednetworksduringmusclewastingincardiaccachexia
AT rolandoarvillacis integrationofmirnaandmrnaexpressionprofilesrevealsmicrornaregulatednetworksduringmusclewastingincardiaccachexia
AT silviarrogatto integrationofmirnaandmrnaexpressionprofilesrevealsmicrornaregulatednetworksduringmusclewastingincardiaccachexia
AT patriciapreis integrationofmirnaandmrnaexpressionprofilesrevealsmicrornaregulatednetworksduringmusclewastingincardiaccachexia
AT maelidalpaisilva integrationofmirnaandmrnaexpressionprofilesrevealsmicrornaregulatednetworksduringmusclewastingincardiaccachexia
AT robsonfcarvalho integrationofmirnaandmrnaexpressionprofilesrevealsmicrornaregulatednetworksduringmusclewastingincardiaccachexia
_version_ 1718384836123557888