Abstract
Background: 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.
Methods: We searched articles indexed in PubMed (MEDLINE), EMBASE and Europe PubMed Central databases using the Medical Subject Heading (MeSH) or Title/Abstract 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.
Results: Observational studies revealed dysregulation of non-coding RNAs in septic patients. Experimental studies confirmed their crosstalk with JNK/NF-kappa B 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.
Conclusions: Although 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.
Methods: We searched articles indexed in PubMed (MEDLINE), EMBASE and Europe PubMed Central databases using the Medical Subject Heading (MeSH) or Title/Abstract 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.
Results: Observational studies revealed dysregulation of non-coding RNAs in septic patients. Experimental studies confirmed their crosstalk with JNK/NF-kappa B 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.
Conclusions: Although 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.
| Original language | English |
|---|---|
| Article number | 383 |
| Number of pages | 12 |
| Journal | Critical Care |
| Volume | 20 |
| Online published | 28 Nov 2016 |
| DOIs | |
| Publication status | Published - 2016 |
| Externally published | Yes |
Funding
This work was supported by the Hong Kong Research Grant Council-General Research Fund (464212, 24115815) and the Food and Health Bureau-Commissioned Research on Control of Infectious Diseases (CU-15-B2) and Health and Medical Research Fund (15140132).
Research Keywords
- Sepsis
- microRNA
- lncRNA
- circRNA
- Biomarker
- Inflammation
- Shock
- NF-KAPPA-B
- RESPIRATORY-DISTRESS-SYNDROME
- INTERNATIONAL CONSENSUS DEFINITIONS
- INFLAMMATORY RESPONSE SYNDROME
- TNF-ALPHA PRODUCTION
- ACUTE LUNG INJURY
- MICRORNA EXPRESSION
- GENE-EXPRESSION
- DOWN-REGULATION
- CARDIAC DYSFUNCTION
Publisher's Copyright Statement
- This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/
