Aberrant miR-219-5p is correlated with TLR4 and serves as a novel biomarker in patients with multiple organ dysfunction syndrome caused by acute paraquat poisoning

Abstract

This study aimed to investigate the clinical significance of serum microRNA-219-5p (miR-219-5p) in patients with multiple organ dysfunction syndrome (MODS) caused by acute paraquat (PQ) poisoning, and its correlation with Toll-like Receptor 4 (TLR4). Luciferase reporter assay was used to investigate in vitro the correlation of miR-219-5p with TLR4. Serum miR-219-5p levels were evaluated by quantitative real-time polymerase chain reaction. Serum levels of TLR4, IL-1β, and TNF-α were measured by Enzyme-linked immune sorbent assay (ELISA). ROC analysis was performed to assess the diagnostic significance, Kaplan-Meier survival curves and Cox regression analysis were used to evaluate the prognostic value of miR-219-5p in MODS patients. TLR4 was a target gene of miR-219-5p and was increased in MODS patients. Serum miR-219-5p level was decreased and negatively correlated with TLR4 level in MODS patients ( r = −0.660, P < 0.001), which had important diagnostic value and negatively correlated with APACHE II score in MODS patients. The miR-219-5p expression was markedly associated with the WBC, ALT, AST, PaCO2, Lac, and APACHE II score. Non-survivals had more patients with low miR-219-5p expression. Patients with low miR-219-5p expression had shorter survival time. MiR-219-5p and APACHE II score were two independently prognostic factors for 28-day survival. MiR-219-5p was negatively correlated with, while TLR4 was positively correlated with the levels of IL-1β and TNF-α. The serum miR-219-5p level may be a potential biomarker for acute PQ-induced MODS diagnosis and prognosis. Furthermore, miR-219-5p may be associated with the progression of MODS by regulating TLR4-related inflammatory response.