The Intricate Role of Non-Coding RNAs in Sepsis-Associated Disseminated Intravascular Coagulation

Disseminated Intravascular Coagulation (DIC) is a type of tissue and organ dysregulation in sepsis, due mainly to the effect of the inflammation on the coagulation system. Unfortunately, the underlying molecular mechanisms that lead to this disorder are not fully understood. Moreover, current biomarkers for DIC, including biological and clinical parameters, generally provide a poor diagnosis and prognosis. In recent years, non-coding RNAs have been studied as promising and robust biomarkers for a variety of diseases. Thus, their potential in the diagnosis and prognosis of DIC should be further studied. Specifically, the relationship between the coagulation cascade and non-coding RNAs should be established. In this review, microRNAs, long non-coding RNAs, and circular RNAs are studied in relation to DIC. Specifically, the axis between these non-coding RNAs and the corresponding affected pathway has been identified, including inflammation, alteration of the coagulation cascade, and endothelial damage. The main affected pathway identified is PI3K/AKT/mTOR axis, where several ncRNAs participate in its regulation, including miR-122-5p which is sponged by circ_0005963, ciRS-122, and circPTN, and miR-19a-3p which is modulated by circ_0000096 and circ_0063425. Additionally, both miR-223 and miR-24 were found to affect the PI3K/AKT pathway and were regulated by lncGAS5 and lncKCNQ1OT1, respectively. Thus, this work provides a useful pipeline of inter-connected ncRNAs that future research on their impact on DIC can further explore.

Automated summary

Disseminated Intravascular Coagulation (DIC) is a type of tissue and organ dysregulation in sepsis, with underlying molecular mechanisms that are not fully understood. Current biomarkers for DIC provide poor diagnosis and prognosis, thus non-coding RNAs are studied as potential biomarkers. This review focuses on the relationship between non-coding RNAs and DIC, particularly the PI3K/AKT/mTOR axis, and identifies several ncRNAs involved in its regulation.