Clinical significance of miR‑181a in patients with neonatal sepsis and its regulatory role in the lipopolysaccharide‑induced inflammatory response

Abstract

Neonatal sepsis (NS) poses a serious threat to the health of neonates worldwide. The present study aimed to investigate the diagnostic value of microRNA (miR)-181a in patients with NS and the regulatory role of miR-181a in lipopolysaccharide (LPS)-induced inflammation. A total of 102 neonates with NS and 50 neonates without sepsis were enrolled in the present study. The serum levels of miR-181a were estimated using reverse transcription-quantitative PCR. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic value of miR-181a for NS. The effect of miR-181a on the expression of Toll-like receptor (TLR)4 was assessed after modification of the expression of miR-181a in monocytes isolated from the blood of neonates in vitro. An ELISA was used to measure the concentration of inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-8 in the supernatant of monocytes. The serum levels of miR-181a were decreased in patients with NS compared with those in the controls. The area under the ROC curve of miR-181a was 0.893 with a sensitivity of 83.3% and a specificity of 84.0%. LPS stimulation in monocytes also led to a decrease in the expression of miR-181a. TLR4 was proven to be a direct target gene of miR-181a, according to the results of a luciferase reporter assay, and overexpression of miR-181a suppressed TLR4 expression in monocytes. Regarding LPS-induced inflammation, it was revealed that the upregulated levels of TNF-α and IL-8 induced by LPS were reduced by overexpression of miR-181a in monocytes. In conclusion, decreased serum levels of miR-181a may serve as a diagnostic biomarker in patients with NS and overexpression of miR-181a inhibits the LPS-induced inflammatory response at least partially by targeting TLR4. Aberrant miR-181a may be a non-invasive biomarker for NS patients, and provide a novel insight into the pathologic mechanisms of action behind the development of NS.

MIR-141 is Negatively Correlated With TLR4 in Neonatal Sepsis and Regulates LPS-induced Inflammatory Responses in Monocytes

“…Ji et al found that Sch B could increase miR-17-5p expression, promote in ammation, and decrease TLR4 expression in sepsis mice and LPS-induced macrophages [29]. The interaction between miR-141 and TLR4 3'-UTR was analyzed by luciferase reporter assay.The results show that TLR4 is the target gene of miR-141.miR-141 plays a role in neonatal sepsis by binding to the 3'-UTR region of TLR4.The mechanism of action of miR-181a in sepsis also con rms this view [30].The results of this study uncover the potential role of miR-141 as a useful potential therapeutic agent in the treatment of sepsisand provide a basis for the application of miR-141 in neonatal sepsis.However, the speci c mechanism of action of miR-141 in neonatal sepsis needs further investigation In short, the abnormal expression of miR-141 is related to the in ammatory response of neonatal sepsis, and miR-141 has a higher diagnostic accuracy in neonatal sepsis.The expression level of miR-141 in LPStreated cells was signi cantly inhibited.It was found that overexpression of miR-141 inhibited LPSinduced in ammation by targeting TLR4 in monocytes.Therefore, increasing the level of miR-141 may be alleviate neonatal sepsis.miR-141 is expected to become a potential diagnostic biomarker and therapeutic target in neonatal sepsis.…”

Accuracy of circulating microRNAs in diagnosis of sepsis: a systematic review and meta-analysis

“…Risk of bias is mainly derived from the index test. The conduct or interpretation of the index test introduced high risk in 6 records [ 7 , 8 , 17 , 19 , 23 , 28 ] and unclear risk in 13 articles [ 6 , 14 – 16 , 18 , 20 , 21 , 25 – 27 , 29 – 31 ].…”

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

“…Accurate diagnosis is the first and most important prerequisite for the efficient treatment of diseases. To improve the treatment of infectious diseases in neonates, it is of value to distinguish cases of NS from neonates with pneumonia/respiratory tract infection ( 30 ). CRP and PCT were established as biomarkers for NS and are widely used for this purpose, but elevated CRP and PCT may also be detected in certain infectious and inflammatory diseases other than NS, such as pneumonia ( 31 ) and respiratory tract infection ( 32 ); thus, their application specificity is limited.…”

“…Zhang et al ( 39 ) suggested that the circulating levels of miR-23b were decreased in patients with sepsis and were able to inhibit the LPS-induced inflammatory response in monocytes. Overexpression of miR-181a inhibited the LPS-induced inflammatory response at least partially by targeting Toll-like receptor 4( 30 ). The present study determined that the expression of miR-1184 was also downregulated in LPS-induced monocytes and overexpression of miR-1184 reversed the promoting effect of LPS on the inflammatory response in monocytes.…”