Abstract
Neonatal sepsis is an inflammatory system syndrome and a main cause of neonatal mortality. However, there is a lack of ideal biomarkers for early neonatal sepsis diagnosis. The aim of this study was to evaluate the clinical significance of miR-141 in sepsis in neonates, and explore the regulatory effects of miR-141 on inflammation in monocytes. This study used qRT-PCR to calculate the expression of miR-141 in the serum of septic neonates. The diagnostic values of procalcitonin (PCT) and serum miR-141 were evaluated by receiver operating characteristic (ROC) curves. The relationship between miR-141 and TLR4 was determined using luciferase reporter assay. An inflammation model was established using monocytes with lipopolysaccharide (LPS) treatment. ELISA assay was used to analyze the levels of pro-inflammatory cytokines. The expression of miR-141 in neonatal sepsis was significantly lower than healthy controls. ROC curves showed that miR-141 had diagnostic accuracy. LPS stimulation in monocytes led to a decrease in the expression of miR-141. A luciferase reporter assay proved that miR-141 targeted TLR4, and a negative correlation of miR-141 with TLR4 was found in septic neonates. ELISA results demonstrated that the overexpression of miR-141 inhibited LPS-induced inflammation in monocytes. In conclusion, serum decreased miR-141 expression served as a candidate diagnostic biomarker of neonatal sepsis. TLR4 is a target gene of miR-141, which may mediate the inhibitory effects of miR-141 overexpression on LPS-induced inflammation in monocytes. Therefore, miR-141 is expected to be a potential diagnostic biomarker and a therapeutic target in neonatal sepsis.
Highlights
Neonatal sepsis is an inflammatory system syndrome caused by infection with bacteria or viruses, which is a main cause of neonatal death [1,2,3]
This study aimed to explore the diagnostic value of miR-141 in neonatal sepsis and its regulatory role in lipopolysaccharide (LPS)-induced inflammation in monocytes
No significant difference was found between septic neonates and controls for age, gender, body weight, white blood cell (WBC) number, and C-reactive protein (CRP)
Summary
Neonatal sepsis is an inflammatory system syndrome caused by infection with bacteria or viruses, which is a main cause of neonatal death [1,2,3]. Researchers have been trying to find the ideal biomarkers with high sensitivity and specificity to diagnose and eliminate neonatal sepsis as early as possible [4]. The most commonly used biomarkers include C-reactive protein (CRP), micro-erythrocyte sedimentation rate, serum amyloid A, and procalcitonin (PCT) [5,6,7]. The clinical application of these molecules is limited, mainly due to poor specificity. No biomarker meets the standard for neonatal sepsis diagnosis [8,9]. Exploring new diagnostic methods and molecular mechanisms is essential for the diagnosis and development of treatment for neonatal sepsis
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