Abstract
BackgroundSepsis coincides with altered gene expression in different tissues. Accumulating evidence has suggested that microRNAs, long non-coding RNAs, and circular RNAs are important molecules involved in the crosstalk with various pathways pertinent to innate immunity, mitochondrial functions, and apoptosis.MethodsWe searched articles indexed in PubMed (MEDLINE), EMBASE and Europe PubMed Central databases using the Medical Subject Heading (MeSH) or Title/ words (“microRNA”, “long non-coding RNA”, “circular RNA”, “sepsis” and/or “septic shock”) from inception to Sep 2016. Studies investigating the role of host-derived microRNA, long non-coding RNA, and circular RNA in the pathogenesis of and as biomarkers or therapeutics in sepsis were included. Data were extracted in terms of the role of non-coding RNAs in pathogenesis, and their applicability for use as biomarkers or therapeutics in sepsis. Two independent researchers assessed the quality of studies using a modified guideline from the Systematic Review Center for Laboratory animal Experimentation (SYRCLE), a tool based on the Cochrane Collaboration Risk of Bias tool.ResultsObservational studies revealed dysregulation of non-coding RNAs in septic patients. Experimental studies confirmed their crosstalk with JNK/NF-κB and other cellular pathways pertinent to innate immunity, mitochondrial function, and apoptosis. Of the included studies, the SYRCLE scores ranged from 3 to 7 (average score of 4.55). This suggests a moderate risk of bias. Of the 10 articles investigating non-coding RNAs as biomarkers, none of them included a validation cohort. Selective reporting of sensitivity, specificity, and receiver operating curve was common.ConclusionsAlthough non-coding RNAs appear to be good candidates as biomarkers and therapeutics for sepsis, their differential expression across tissues complicated the process. Further investigation on organ-specific delivery of these regulatory molecules may be useful.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1555-3) contains supplementary material, which is available to authorized users.
Highlights
Sepsis coincides with altered gene expression in different tissues
MiRNAs are essential for the production of proinflammatory tumor necrosis factor (TNF)-α and interleukin (IL)-1β via p38 mitogen-activated protein kinase (MAPK) and MAPK phosphatase 1 (MKP-1) pathways [6,7,8,9, 12,13,14]
In case-control studies, differential expression of miRNAs was detected in patients with sepsis compared to controls, suggesting that miRNAs may be used as biomarkers for diagnosis and prognostic stratification or as therapeutic targets [8, 12, 15,16,17,18,19,20,21]
Summary
Sepsis coincides with altered gene expression in different tissues. Accumulating evidence has suggested that microRNAs, long non-coding RNAs, and circular RNAs are important molecules involved in the crosstalk with various pathways pertinent to innate immunity, mitochondrial functions, and apoptosis. Sepsis is defined as the presence of a life-threatening organ dysfunction as a result of altered systemic host response to an infection [1, 2]. This leads to multiple organ failure and superimposed secondary infections. Ho et al Critical Care (2016) 20:383 regions of target mRNAs, miRNAs regulate a range of genes post-transcriptionally [10]. These regulatory polynucleotides play dual roles, either protective or detrimental, in cancers, neurodegenerative diseases, and immune-related diseases [11]. In case-control studies, differential expression of miRNAs was detected in patients with sepsis compared to controls, suggesting that miRNAs may be used as biomarkers for diagnosis and prognostic stratification or as therapeutic targets [8, 12, 15,16,17,18,19,20,21]
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