Long noncoding RNA and messenger RNA abnormalities in pediatric sepsis: a preliminary study

Abstract

Background: Sepsis represents a complex disease with dysregulated inflammatory response and high mortality rate. Long noncoding RNAs (lncRNAs) have been reported to play regulatory roles in a variety of biological processes. However, studies evaluating the function of lncRNAs in pediatric sepsis are scarce, and current knowledge of the role of lncRNAs in pediatric sepsis is still limited. The present study explored the expression patterns of both lncRNAs and mRNAs between pediatric sepsis patients and healthy controls based on a comprehensive microarray analysis. Methods: LncRNA and mRNA microarray was used to detect the expression of lncRNAs and mRNAs in the septic and control groups. Aberrantly expressed mRNAs and lncRNAs identified were further interpreted by enrichment analysis, receiver operating characteristic (ROC) curve analysis, co-expression network analysis, and quantitative realtime PCR (qPCR). Results: A total of 1488 differetially expressed lncRNAs and 1460 differentially expressed mRNAs were identified. A co-expression network of the identified lncRNAs and mRNAs was constructed. In this network, lncRNA lnc-RP11-1220 K2.2.1-7 is correlated with mRNA CXCR1 and CLEC4D; lncRNA lnc-ANXA3-2 is correlated with mRNA CLEC4D; lncRNA lnc-TRAPPC5-1 is correlated with mRNA DYSF and HLX; lncRNA lnc-ZNF638-1 is correlated with mRNA DYSF and HLX. Significantly different expressions between pediatric sepsis patients and controls were validated by qPCR for the 4 lncRNAs and 4 co-expressed mRNAs, validating the microarray results. Conclusions: Our study contributes to a comprehensive understading of the involvment of lncRNAs and mRNAs in pediatric sepsis, which may guide subsequent experimental research. Furthermore, our study may also provide potential candidate lncRNAs and mRNAs for the diagnosis and treatment of pediatric sepsis.

Dysregulated lncRNAs are Involved in the Progress of Sepsis by Constructing Regulatory Networks in Whole Blood Cells

“…Likewise, high lncRNA NEAT1 expression showed close correlation with increased disease risk, enhanced severity, and higher 28-day mortality in sepsis (Yang et al, 2020). Bai et al (Bai et al, 2020) also identified four pediatric sepsisassociated lncRNAs, including RP11-1220 K2.2.1-7, ANXA3-2, TRAPPC5-1, and ZNF638-1. These lncRNAs were significantly highly expressed in septic children and could be novel biomarkers for pediatric sepsis.…”

“…Of these, 1,146 lncRNAs were specifically detected in sepsis groups, suggesting that lncRNAs were globally activated in sepsis samples. Previous studies have suggested that lncRNAs may be potential biomarkers for prognosis of sepsis, such as lncRNAs MALAT1, NEAT1, RP11-1220 K2.2.1-7, ANXA3-2, TRAPPC5-1, and ZNF638-1 (Chen et al, 2018a;Geng et al, 2019;Bai et al, 2020), which have been introduced in introduction. Herein, the PCA result showed sepsis and control specimens could be separated by the second component, providing the solid evidence that lncRNAs could be diagnostic biomarkers to distinguish sepsis from no_sepsis and control specimens.…”

“…Due to the properties of participating in chromatin rearrangement, histone modification, and modification of alternative splicing genes, as well as the regulation of gene expression, lncRNAs have emerged as important factors contributing to the development and progression of various diseases (Esteller, 2011;Schonrock et al, 2012;Beermann et al, 2016;Gu et al, 2018;Zhang et al, 2019a). As a benefit from the advance of next-generation sequencing technology, a limited number of sepsis-associated lncRNAs had been identified (Cui et al, 2014;Du et al, 2017;Pellegrina et al, 2017;Zhang et al, 2019b;Bai et al, 2020). Geng et al (Geng et al, 2019) demonstrated that lncRNA MALAT1 expression was elevated in adults with sepsis and suggested lncRNA MALAT1 could be developed as a potential biomarker for facilitating diagnosis and management in sepsis.…”

Long Noncoding RNA: Regulatory Mechanisms and Therapeutic Potential in Sepsis

“…In addition, Wang et al reported that miR-15a/16 was up-regulated in serum of patients with neonatal sepsis; investigations into its mechanism revealed that lncRNA SHNG16 could act as a ceRNA and positively regulate TLR4 by competitively binding miR-15a/16 in LPS-induced macrophages, thus indicating that lncRNA SNHG16 affected inflammatory responses in neonatal sepsis (Wang et al, 2018). Apart from neonatal sepsis, Bai et al reported a total of 1,488 DE lncRNAs and 1,460 DE mRNAs between ten pediatric patients with sepsis and twelve healthy controls; they conducted a co-expression network analysis of the DE lncRNAs and mRNAs, suggesting a correlation between lncRNA and mRNA expression that were involved in the pathogenesis of sepsis (Bai et al, 2020). Considering the different pathophysiological processes between children and adult sepsis (Weiss et al, 2020), further research is needed to elucidate the roles of lncRNAs and explore their molecular mechanisms in children with sepsis.…”

“…Apart from neonatal sepsis, Bai et al. reported a total of 1,488 DE lncRNAs and 1,460 DE mRNAs between ten pediatric patients with sepsis and twelve healthy controls; they conducted a co-expression network analysis of the DE lncRNAs and mRNAs, suggesting a correlation between lncRNA and mRNA expression that were involved in the pathogenesis of sepsis ( Bai et al., 2020 ). Considering the different pathophysiological processes between children and adult sepsis ( Weiss et al., 2020 ), further research is needed to elucidate the roles of lncRNAs and explore their molecular mechanisms in children with sepsis.…”