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异常长非编码 RNA 癌症易感性 15(CASC15)在新生儿败血症中作为诊断生物标志物并调节炎症反应。

Aberrant long non-coding RNA cancer susceptibility 15 (CASC15) plays a diagnostic biomarker and regulates inflammatory reaction in neonatal sepsis.

机构信息

Department of Neonatology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, 250021, China.

出版信息

Bioengineered. 2021 Dec;12(2):10373-10381. doi: 10.1080/21655979.2021.1996514.

Abstract

Neonatal sepsis (NS) is one of the important causes of neonatal death. There are many studies to confirm the role of long non-coding RNA (lncRNA) in neonatal infectious diseases. This study aimed to explore the level of cancer susceptibility 15 (CASC15) and its effect on inflammatory response in NS. Seventy-nine neonatal pneumonia (NP) patients and 80 NS patients were enrolled in this study. Reverse Transcription-quantitative PCR (RT-qPCR) was used to determine the expression levels of CASC15 and miR-144-3p. Receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic value of CASC15 in NS. RAW264.7 cells were stimulated with LPS to simulate the inflammatory response in NS patients, and the regulation and mechanism of CASC15 on the inflammatory response were explored in this in vitro cell model. Serum CASC15 was upregulated in NS patients, and it had the ability to distinguish NS patients from NP patients. LPS stimulation increased the expression of CASC15 and simultaneously stimulated the secretion of inflammatory cytokines, while the knockdown of CASC15 alleviated the inflammatory response induced by LPS stimulation. Besides, serum miR-144-3p was reduced in NS patients, and luciferase reporter genes showed that miR-144-3p was a direct target of CASC15. Overexpression of CASC15 may promote the inflammatory response of NS by targeted regulating the expression of miR-144-3p, which may provide us with new insights in the treatment of NS.

摘要

新生儿败血症(NS)是新生儿死亡的重要原因之一。有许多研究证实长链非编码 RNA(lncRNA)在新生儿感染性疾病中的作用。本研究旨在探讨抑癌基因 15(CASC15)的水平及其对 NS 炎症反应的影响。本研究纳入了 79 例新生儿肺炎(NP)患者和 80 例 NS 患者。采用逆转录定量 PCR(RT-qPCR)测定 CASC15 和 miR-144-3p 的表达水平。绘制受试者工作特征(ROC)曲线评估 CASC15 在 NS 中的诊断价值。用 LPS 刺激 RAW264.7 细胞模拟 NS 患者的炎症反应,探讨 CASC15 对炎症反应的调节作用及其机制。在 NS 患者中血清 CASC15 上调,并具有区分 NS 患者和 NP 患者的能力。LPS 刺激增加了 CASC15 的表达,同时刺激了炎症细胞因子的分泌,而 CASC15 的敲低减轻了 LPS 刺激引起的炎症反应。此外,NS 患者血清 miR-144-3p 降低,荧光素酶报告基因显示 miR-144-3p 是 CASC15 的直接靶标。CASC15 的过表达可能通过靶向调节 miR-144-3p 的表达促进 NS 的炎症反应,这可能为 NS 的治疗提供新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f857/8809971/4c97c8747a13/KBIE_A_1996514_F0001_B.jpg

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