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Diagnostic Value of miR-103 in Patients with Sepsis and Noninfectious SIRS and Its Regulatory Role in LPS-Induced Inflammatory Response by Targeting TLR4.
International Journal of Genomics ( IF 2.6 ) Pub Date : 2020-05-13 , DOI: 10.1155/2020/2198308
Min Yang 1 , Li Zhao 2 , Mingyan Sun 3
Affiliation  

Background. Sepsis is a life-threatening condition and a systemic inflammatory response syndrome (SIRS) driven by infection. This study aimed at investigating the expression of microRNA-103 (miR-103) in sepsis patients, evaluating its diagnostic value, and exploring the regulatory effect of miR-103 on LPS-induced inflammation in monocytes. Methods. Expression of miR-103 was measured using quantitative real-time PCR. A receiver operating characteristics curve was plotted to evaluate the diagnostic vale of miR-103. Serum and cell supernatant levels of proinflammatory cytokines were analyzed using ELISA. The interaction between miR-103 and Toll-like receptors 4 (TLR4) was analyzed using luciferase reporter assay. The effect of miR-103 on inflammation was examined in LPS-treated monocytes. Results. Serum expression of miR-103 was decreased in noninfectious SIRS and sepsis patients compared with healthy controls, and the lowest expression value was observed in sepsis patients (all ). Serum levels of miR-103 have considerable diagnostic accuracy in distinguishing sepsis patients from SIRS patients and healthy controls. A negative correlation was found between miR-103 and inflammatory responses in sepsis patients. TLR4 was demonstrated to be a direct target of miR-103 and was negatively regulated by miR-103 in monocytes. The promoted inflammatory responses by LPS in monocytes were reversed by the overexpression of miR-103. Conclusion. All the data revealed that serum decreased miR-103 in sepsis patients serves as a promising noninvasive diagnostic biomarker and may be involved in the pathogenesis of sepsis by regulating inflammatory responses via targeting TLR4.

中文翻译:

miR-103 在脓毒症和非感染性 SIRS 患者中的诊断价值及其靶向 TLR4 在 LPS 诱导的炎症反应中的调节作用。

背景。脓毒症是一种危及生命的疾病,是一种由感染驱动的全身炎症反应综合征 (SIRS)。本研究旨在调查microRNA-103(miR-103)在脓毒症患者中的表达,评估其诊断价值,并探索miR-103对LPS诱导的单核细胞炎症的调节作用。方法。使用定量实时 PCR 测量 miR-103 的表达。绘制受试者工作特征曲线以评估 miR-103 的诊断价值。使用ELISA分析促炎细胞因子的血清和细胞上清液水平。使用荧光素酶报告基因分析分析 miR-103 和 Toll 样受体 4 (TLR4) 之间的相互作用。在 LPS 处理的单核细胞中检查了 miR-103 对炎症的影响。结果。与健康对照相比,非感染性 SIRS 和脓毒症患者的血清 miR-103 表达降低,脓毒症患者的表达值最低(所有)。miR-103 的血清水平在区分脓毒症患者与 SIRS 患者和健康对照方面具有相当大的诊断准确性。发现 miR-103 与脓毒症患者的炎症反应呈负相关。TLR4 被证明是 miR-103 的直接靶标,并且在单核细胞中受到 miR-103 的负调控。LPS 在单核细胞中促进的炎症反应被 miR-103 的过表达逆转。结论。所有数据显示,脓毒症患者血清中 miR-103 降低可作为一种有前途的非侵入性诊断生物标志物,并可能通过靶向 TLR4 调节炎症反应参与脓毒症的发病机制。
更新日期:2020-05-13
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