Use of miRNAs as biomarkers in sepsis

Abstract

Sepsis is one of the most common causes of death in critical patients. Severe generalized inflammation, infections, and severe physiological imbalances significantly decrease the survival rate with more than 50%. Moreover, monitoring, evaluation, and therapy management often become extremely difficult for the clinician in this type of patients. Current methods of diagnosing sepsis vary based especially on the determination of biochemical-humoral markers, such as cytokines, components of the complement, and proinflammatory and anti-inflammatory compounds. Recent studies highlight the use of new biomarkers for sepsis, namely, miRNAs. miRNAs belong to a class of small, noncoding RNAs with an approximate content of 19-23 nucleotides. Following biochemical and physiological imbalances, the expression of miRNAs in blood or other body fluids changes significantly. Moreover, its stability, specificity, and selectivity make miRNAs ideal candidates for sepsis biomarkers. In conclusion, we can affirm that stable species of circulating miRNAs represent potential biomarkers for monitoring the evolution of sepsis.

Figure 1

miRNA biogenesis mechanism. miRNA synthesis begins with RNA polymerase II action on protein coding genes. (a) Through the transformation phenomenon of the miRNAs genes, pri-miRNA is forming. (b) By the action of RNase III endonuclease (Drosha) and of the DiGeorge Syndrome Critical Region 8 (DGCR8) cofactor, the pre-miRNA is forming. (c) Through transporting protein Exportin-5, pre-miRNA is transferred from the nucleus into the cytoplasm. (d) In the cytoplasm pre-miRNA is attacked by second RNase III endonuclease (Dicer) and transactivator RNA binding protein forming mature miRNA (double-stranded) and miRNA^∗ (passenger strand). In what follows, mature miRNA induced silencing is taken in complex (RISC). RISC complex contains mature miRNA and protein Argonaute 2 (AGO) that confers increased stability of the complex. After this, miRNAs are released from the cell by two mechanisms: active release (microvesicles, exosomes, and high density lipoprotein particles) and passive release (apoptotic bodies).