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长链非编码RNA HCP5作为一种潜在的诊断生物标志物,通过靶向miR-138-5p/SIRT1减轻新生儿败血症中的炎症反应。

LncRNA HCP5 acts as a potential diagnostic biomarker and attenuates the inflammatory response in neonatal sepsis by targeting miR-138-5p/SIRT1.

作者信息

Hu Xiaohua, Hu Anhui, Luo Yong, Yuan Shuisheng, Yang Lei

机构信息

Department of Neonatology, Maternity & Child Care Center of Xinyu, Xinyu 338025, China.

出版信息

Cent Eur J Immunol. 2024;49(3):216-226. doi: 10.5114/ceji.2024.143462. Epub 2024 Sep 27.

Abstract

INTRODUCTION

This study aimed to investigate the clinical significance and potential mechanism of long non-coding RNA human histocompatibility leukocyte antigen complex P5 (HCP5) in neonatal sepsis (NS).

MATERIAL AND METHODS

The study enrolled 86 patients with NS and 80 neonates with respiratory tract infection or pneumonia. The Pearson correlation coefficient was used to evaluate the association of procalcitonin (PCT), C-reactive protein (CRP), and inflammatory factors with HCP5. Serum levels of HCP5 were measured using RT-qPCR. The diagnostic potential of HCP5 was assessed via a receiver operating characteristic (ROC) curve. An in vitro model was established using lipopolysaccharide (LPS)-induced RAW264.7 macrophages. ELISA was conducted to measure the levels of inflammatory factors. Finally, the target relationship was validated using a dual-luciferase reporter assay.

RESULTS

HCP5 was significantly lower in patients with NS and it negatively correlated with PCT, CRP, interleukin (IL)-8, and tumor necrosis factor (TNF-). The area under the ROC curve was 0.902, and the sensitivity and specificity for identifying NS from controls were 86.30% and 83.72%, respectively. In LPS-induced RAW264.7, the levels of HCP5 decreased in a time- and dose-dependent manner. miR-138-5p, a target miRNA for HCP5, was found to be elevated in NS patients. Furthermore, HCP5 significantly reduced LPS-induced overproduction of inflammatory factors, but miR-138-5p reversed this reduction. Furthermore, sirtuin 1 (SIRT1) is a downstream target of miR-138-5p.

CONCLUSIONS

HCP5 could potentially serve as a diagnostic biomarker for NS and it may inhibit inflammation in NS by targeting miR-138-5p/SIRT1 axis. These findings highlight the potential role of HCP5 in the diagnosis and treatment of NS.

摘要

引言

本研究旨在探讨长链非编码RNA人组织相容性白细胞抗原复合物P5(HCP5)在新生儿败血症(NS)中的临床意义及潜在机制。

材料与方法

本研究纳入了86例NS患者以及80例患有呼吸道感染或肺炎的新生儿。采用Pearson相关系数评估降钙素原(PCT)、C反应蛋白(CRP)及炎症因子与HCP5的相关性。采用逆转录定量聚合酶链反应(RT-qPCR)检测血清HCP5水平。通过绘制受试者工作特征(ROC)曲线评估HCP5的诊断潜力。利用脂多糖(LPS)诱导的RAW264.7巨噬细胞建立体外模型。采用酶联免疫吸附测定(ELISA)检测炎症因子水平。最后,通过双荧光素酶报告基因检测验证靶标关系。

结果

NS患者的HCP5水平显著降低,且与PCT、CRP、白细胞介素(IL)-8及肿瘤坏死因子(TNF)-呈负相关。ROC曲线下面积为0.902,从对照组中鉴别出NS的灵敏度和特异度分别为86.30%和83.72%。在LPS诱导的RAW264.7细胞中,HCP5水平呈时间和剂量依赖性降低。发现NS患者中HCP5的靶标微小RNA(miRNA)miR-138-5p升高。此外,HCP5显著降低LPS诱导的炎症因子过量产生,但miR-138-5p可逆转这种降低作用。此外,沉默调节蛋白1(SIRT1)是miR-138-5p的下游靶标。

结论

HCP5可能作为NS的诊断生物标志物,并且可能通过靶向miR-138-5p/SIRT1轴抑制NS中的炎症反应。这些发现凸显了HCP5在NS诊断和治疗中的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ba/11664802/b8d1a88f1d1f/CEJI-49-54870-g001.jpg

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