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

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

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Resumé

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.

OriginalsprogEngelsk
Artikelnummer6998
TidsskriftScientific Reports
Vol/bind7
Udgave nummer1
Antal sider14
ISSN2045-2322
DOI
StatusUdgivet - 1. aug. 2017

Fingeraftryk

MicroRNAs
Muscles
Messenger RNA
Gene Ontology
Citric Acid Cycle
Gene Expression Profiling
Proteasome Endopeptidase Complex
Electron Transport
Proteolysis
Skeletal Muscle
Down-Regulation

Citer dette

Moraes, L. N., Fernandez, G. J., Vechetti-Júnior, I. J., Freire, P. P., Souza, R. W. A., Villacis, R. A. R., ... Carvalho, R. F. (2017). Integration of miRNA and mRNA expression profiles reveals microRNA-regulated networks during muscle wasting in cardiac cachexia. Scientific Reports, 7(1), [6998]. https://doi.org/10.1038/s41598-017-07236-2
Moraes, Leonardo N ; Fernandez, Geysson J ; Vechetti-Júnior, Ivan J ; Freire, Paula P ; Souza, Rodrigo W A ; Villacis, Rolando A R ; Rogatto, Silvia R ; Reis, Patricia P ; Dal-Pai-Silva, Maeli ; Carvalho, Robson F. / Integration of miRNA and mRNA expression profiles reveals microRNA-regulated networks during muscle wasting in cardiac cachexia. I: Scientific Reports. 2017 ; Bind 7, Nr. 1.
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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.",
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Moraes, LN, Fernandez, GJ, Vechetti-Júnior, IJ, Freire, PP, Souza, RWA, Villacis, RAR, Rogatto, SR, Reis, PP, Dal-Pai-Silva, M & Carvalho, RF 2017, 'Integration of miRNA and mRNA expression profiles reveals microRNA-regulated networks during muscle wasting in cardiac cachexia', Scientific Reports, bind 7, nr. 1, 6998. https://doi.org/10.1038/s41598-017-07236-2

Integration of miRNA and mRNA expression profiles reveals microRNA-regulated networks during muscle wasting in cardiac cachexia. / Moraes, Leonardo N; Fernandez, Geysson J; Vechetti-Júnior, Ivan J; Freire, Paula P; Souza, Rodrigo W A; Villacis, Rolando A R; Rogatto, Silvia R; Reis, Patricia P; Dal-Pai-Silva, Maeli; Carvalho, Robson F.

I: Scientific Reports, Bind 7, Nr. 1, 6998, 01.08.2017.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Integration of miRNA and mRNA expression profiles reveals microRNA-regulated networks during muscle wasting in cardiac cachexia

AU - Moraes, Leonardo N

AU - Fernandez, Geysson J

AU - Vechetti-Júnior, Ivan J

AU - Freire, Paula P

AU - Souza, Rodrigo W A

AU - Villacis, Rolando A R

AU - Rogatto, Silvia R

AU - Reis, Patricia P

AU - Dal-Pai-Silva, Maeli

AU - Carvalho, Robson F

PY - 2017/8/1

Y1 - 2017/8/1

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1038/s41598-017-07236-2

DO - 10.1038/s41598-017-07236-2

M3 - Journal article

C2 - 28765595

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 6998

ER -