Downregulation of miR‑1184 serves as a diagnostic biomarker in neonatal sepsis and regulates LPS‑induced inflammatory response by inhibiting IL‑16 in monocytes

Abstract

Neonatal sepsis (NS) remains a global problem. In the present study, abnormal expression of microRNA-1184 (miR-1184) was detected in neonates with NS and it was endeavored to investigate the diagnostic value of miR-1184, as well as its regulatory role in lipopolysaccharide (LPS)-induced inflammatory response in vitro. Furthermore, the correlation between interleukin-16 (IL-16) and miR-1184 was investigated to elucidate the pathological mechanisms of NS development. Reverse transcription-quantitative PCR was used to detect the expression of miR-1184. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic value of miR-1184 in NS. Furthermore, a sepsis cell model was established by using LPS-induced monocytes to explore the effect of miR-1184 on the inflammatory response. The levels of inflammatory cytokines were determined by ELISA. A luciferase reporter assay was used to investigate the direct targeting interaction between miR-1184 and IL-16. The results indicated that the serum levels of miR-1184 in neonates with sepsis were decreased and miR-1184 had a high diagnostic value when differentiating NS from respiratory conditions in neonates. In vitro, the expression of miR-1184 in monocytes was inhibited by LPS and overexpression of miR-1184 reversed the effect of LPS to stimulate the inflammatory response. IL-16 was demonstrated to be a target of miR-1184 and a negative correlation between them was identified in patients with NS. The inflammatory response inhibited by miR-1184 mimics was enhanced by overexpression of IL-16 in LPS-induced monocytes. In conclusion, decreased levels of serum miR-1184 may be a potential diagnostic biomarker for NS. In addition, miR-1184 inhibited the LPS-induced inflammatory response by targeting IL-16 in monocytes, suggesting that the miR-1184/IL-16 axis may be a potential therapeutic target for NS.

miR-486-5p Serves as a Diagnostic Biomarker for Sepsis and Its Predictive Value for Clinical Outcomes

“… 29 Although blood culture is the gold standard for sepsis, identification is complicated by high false-negative results. 6 The APACHE II score and SOFA score are widely used to assess sepsis risk and prognosis; however, multiple measurements are required due to their poor specificity. 30 Therefore, we analyzed the correlation between serum miR-486-5p and common diagnostic criteria PCT, CRP, APACHE II, and SOFA score by Spearman coefficient analysis.…”

“…Abnormal expression of miRNAs is not only participated in the important biological functions of disease but also proposed as a diagnostic and predictive biomarker due to its conservation and stability. 5 As the abnormal miR-1184, 6 miR-22-3p, 7 and miR-452 8 have been proved to be potential biomarkers of sepsis. Among many miRNAs, miR-486-5p is located on human chromosome 8p11.21 and can be used as a potential biomarker for sarcopenia in the elderly, 9 endometrial cancer, 10 and chronic myelogenous leukemia.…”

Serum miR-34a-5p and miR-199a-3p as new biomarkers of neonatal sepsis

“…Increasing evidence suggests that miRNAs play vital roles in immune regulation in autoimmune and infectious diseases [ 22 , 23 ]. Various biomarkers have been considered to aid the diagnosis and prognosis of sepsis, but with limitations in severe and early cases [ 2 , 3 ]. Recently, much attention has focused on utilizing serum miRNAs as biomarkers for the diagnosis and prognosis of sepsis that are released outside cells into serum and remain stable in circulation, given their ease of detection [ 24 ].…”

“…Numerous biomarkers for the diagnosis and detection of sepsis at an early stage have been identified, such as C-reactive protein (CRP), procalcitonin (PCT), and interleukins (ILs), but they have poor specificity [ 2 ]. Blood culture is widely used in the diagnosis of sepsis, but the results of culture may be delayed and false negative results are often obtained [ 3 – 5 ]. Therefore, there is an urgent need to identify novel biomarkers for discriminating sepsis at an early stage in addition to the possibility of their use as therapeutic targets.…”

MicroRNA as an Early Biomarker of Neonatal Sepsis

“…Lastly, Wang et al have shown significant downregulation of miR-1184 in septic neonates and correlation with levels of serum pro-inflammatory cytokines Il-1β, IL-6, and TNF-α. Artificial overexpression of this miRNA improved inflammatory response in LPS-induced monocytes ( 75 ).…”