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长链非编码RNA EPB41L4A-AS1作为脓毒症的生物标志物,通过靶向miR-146a-5p减轻炎症反应。

Long non-coding RNA EPB41L4A-AS1 as a biomarker of sepsis alleviates inflammatory response by targeting miR-146a-5p.

作者信息

Zhou Weigui, Li Chan, Yun Huixian, Zhang Ningning, Zhang Rui

机构信息

Department of Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China.

Department of Emergency, People's Hospital of Yubei District Chongqing City, Chongqing, 401120, China.

出版信息

Eur J Med Res. 2025 Aug 11;30(1):728. doi: 10.1186/s40001-025-02991-9.

DOI:10.1186/s40001-025-02991-9
PMID:40790247
Abstract

OBJECTIVE

The prognosis of sepsis, a pathological condition associated with high mortality and rapid progression, can be improved with precise diagnosis, effective treatment, and nursing care. This study investigated the expression and clinical significance of the long non-coding RNA (lncRNA) EPB41L4A-AS1 in sepsis.

METHODS

The serum EPB41L4A-AS1 levels in patients with sepsis were quantified using quantitative real-time polymerase chain reaction (RT-qPCR). The diagnostic value of EPB41L4A-AS1 was determined using the receiver operating characteristic curves. The correlation of EPB41L4A-AS1 with clinical parameters was evaluated using Pearson correlation. Kaplan-Meier assessment of prognostic value. Lipopolysaccharide (LPS)-treated THP-1 cells served as an in vitro cell model for sepsis. The mRNA and protein levels of inflammatory factors were examined using RT-qPCR analysis and enzyme-linked immunosorbent assay, respectively. Finally, the binding of EPB41L4A-AS1 to miR-146a-5p was determined using the dual-luciferase reporter and RNA immunoprecipitation assays.

RESULTS

EPB41L4A-AS1 was significantly downregulated in patients with sepsis. The downregulation was inversely correlated with inflammatory cytokines and severity scores (APACHE II and SOFA). EPB41L4A-AS1 expression had a high diagnostic value in sepsis. The overexpression of EPB41L4A-AS1 downregulated inflammatory factor expression and release. However, miR-146a-5p mitigated the inhibitory effects of EPB41L4A-AS1 overexpression on inflammatory factors expression and release. EPB41L4A-AS1 was a target of miR-146a-5p.

CONCLUSION

lncRNA EPB41L4A-AS1 alleviates sepsis-related inflammation by targeting miR-146a-5p and may serve as a diagnostic biomarker for sepsis.

摘要

目的

脓毒症是一种死亡率高且进展迅速的病理状态,精确诊断、有效治疗及护理可改善其预后。本研究调查了长链非编码RNA(lncRNA)EPB41L4A-AS1在脓毒症中的表达及临床意义。

方法

采用定量实时聚合酶链反应(RT-qPCR)定量脓毒症患者血清中EPB41L4A-AS1水平。使用受试者工作特征曲线确定EPB41L4A-AS1的诊断价值。采用Pearson相关性评估EPB41L4A-AS1与临床参数的相关性。采用Kaplan-Meier法评估预后价值。用脂多糖(LPS)处理的THP-1细胞作为脓毒症的体外细胞模型。分别采用RT-qPCR分析和酶联免疫吸附测定法检测炎症因子的mRNA和蛋白水平。最后,采用双荧光素酶报告基因和RNA免疫沉淀试验确定EPB41L4A-AS1与miR-146a-5p的结合情况。

结果

脓毒症患者中EPB41L4A-AS1显著下调。下调与炎症细胞因子及严重程度评分(APACHE II和SOFA)呈负相关。EPB41L4A-AS1表达在脓毒症中具有较高诊断价值。EPB41L4A-AS1过表达下调炎症因子表达和释放。然而,miR-146a-5p减轻了EPB41L4A-AS1过表达对炎症因子表达和释放的抑制作用。EPB41L4A-AS1是miR-146a-5p的靶标。

结论

lncRNA EPB41L4A-AS1通过靶向miR-146a-5p减轻脓毒症相关炎症,可能作为脓毒症的诊断生物标志物。

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