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Non-Coding RNA 2017, 3(1), 5; doi:10.3390/ncrna3010005

Insights into the Function of Long Noncoding RNAs in Sepsis Revealed by Gene Co-Expression Network Analysis

1
Programa Interunidades de Pós-Graduação em Bioinformática, Universidade de São Paulo, 05508-090 São Paulo, Brazil
2
Instituto Israelita de Ensino e Pesquisa, Hospital Israelita Albert Einstein, 05652-900 São Paulo, Brazil
3
Departamento de Emergências Clínicas, Faculdade de Medicina da Universidade de São Paulo, 05403-000 São Paulo, Brazil
4
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, 05508-000 São Paulo, Brazil
*
Author to whom correspondence should be addressed.
Received: 1 November 2016 / Accepted: 20 January 2017 / Published: 26 January 2017
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Abstract

Sepsis is a major cause of death and its incidence and mortality increase exponentially with age. Most gene expression studies in sepsis have focused in protein-coding genes and the expression patterns, and potential roles of long noncoding RNAs (lncRNAs) have not been investigated yet. In this study, we performed co-expression network analysis of protein-coding and lncRNAs measured in neutrophil granulocytes from adult and elderly septic patients, along with age-matched healthy controls. We found that the genes displaying highest network similarity are predominantly differently expressed in sepsis and are enriched in loci encoding proteins with structural or regulatory functions related to protein translation and mitochondrial energetic metabolism. A number of lncRNAs are strongly connected to genes from these pathways and may take part in regulatory loops that are perturbed in sepsis. Among those, the ribosomal pseudogenes RP11-302F12.1 and RPL13AP7 are differentially expressed and appear to have a regulatory role on protein translation in both the elderly and adults, and lncRNAs MALAT1, LINC00355, MYCNOS, and AC010970.2 display variable connection strength and inverted expression patterns between adult and elderly networks, suggesting that they are the best candidates to be further studied to understand the mechanisms by which the immune response is impaired by age. In summary, we report the expression of lncRNAs that are deregulated in patients with sepsis, including subsets that display hub properties in molecular pathways relevant to the disease pathogenesis and that may participate in gene expression regulatory circuits related to the poorer disease outcome observed in elderly subjects. View Full-Text
Keywords: sepsis; aging; inflammation; transcriptome; long noncoding RNAs; co-expression networks sepsis; aging; inflammation; transcriptome; long noncoding RNAs; co-expression networks
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Pellegrina, D.V.S.; Severino, P.; Barbeiro, H.V.; de Souza, H.P.; Machado, M.C.C.; Pinheiro-da-Silva, F.; Reis, E.M. Insights into the Function of Long Noncoding RNAs in Sepsis Revealed by Gene Co-Expression Network Analysis. Non-Coding RNA 2017, 3, 5.

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