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miR-9 在调节 COVID-19 患者 NF-κB 信号和细胞因子表达中的作用。

Role of miR-9 in Modulating NF-κB Signaling and Cytokine Expression in COVID-19 Patients.

机构信息

Department for the Promotion of Human Sciences and Quality of Life, San Raffaele University, Via di Val Cannuta 247, 00166 Rome, Italy.

Laboratory of Microbiology, IRCCS San Raffaele Roma, Via di Val Cannuta 247, 00166 Rome, Italy.

出版信息

Int J Mol Sci. 2024 Aug 16;25(16):8930. doi: 10.3390/ijms25168930.

DOI:10.3390/ijms25168930
PMID:39201618
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11354618/
Abstract

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has had a significant impact on global health, with severe cases often characterized by a worsening cytokine storm. Since it has been described that the NF-κB signaling pathway, regulated by microRNAs, could play a pivotal role in the inflammatory response, in this study, the role of miR-9 in modulating NF-κB signaling and inflammatory cytokine expression in COVID-19 patients was investigated. This observational retrospective single-center study included 41 COVID-19 patients and 20 healthy controls. Serum samples were analyzed for miR-9, NF-κB, and IκBα expression levels using RT-PCR. The expression levels and production of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α were measured using RT-PCR and ELISA. Statistical analyses, including correlation and regression, were conducted to explore relationships between these variables. COVID-19 patients, particularly non-survivors, exhibited significantly higher miR-9 and NF-κB levels compared to controls. A strong positive correlation was found between miR-9 and NF-κB expression (r = 0.813, < 0.001). NF-κB levels were significantly correlated with IL-6 (r = 0.971, < 0.001), IL-1β (r = 0.968, < 0.001), and TNF-α (r = 0.968, < 0.001). Our findings indicate that miR-9 regulates NF-κB signaling and inflammation in COVID-19. Elevated miR-9 levels in non-survivors suggest its potential as a severity biomarker. While COVID-19 cases have decreased, targeting miR-9 and NF-κB could improve outcomes for other inflammatory conditions, including autoimmune diseases, highlighting the need for continued research in this area.

摘要

新型冠状病毒病(COVID-19)由 SARS-CoV-2 病毒引起,对全球健康造成了重大影响,严重病例常伴有细胞因子风暴加重。由于已描述 NF-κB 信号通路受 microRNA 调控,可能在炎症反应中发挥关键作用,因此在这项研究中,研究人员调查了 miR-9 在调节 COVID-19 患者的 NF-κB 信号和炎症细胞因子表达中的作用。这项观察性回顾性单中心研究纳入了 41 例 COVID-19 患者和 20 名健康对照者。使用 RT-PCR 分析血清样本中 miR-9、NF-κB 和 IκBα 的表达水平。使用 RT-PCR 和 ELISA 测量促炎细胞因子 IL-6、IL-1β 和 TNF-α的表达水平和产生。进行了统计分析,包括相关性和回归,以探讨这些变量之间的关系。与对照组相比,COVID-19 患者,特别是非幸存者,miR-9 和 NF-κB 水平显著升高。miR-9 与 NF-κB 表达之间存在强烈的正相关(r=0.813,<0.001)。NF-κB 水平与 IL-6(r=0.971,<0.001)、IL-1β(r=0.968,<0.001)和 TNF-α(r=0.968,<0.001)显著相关。研究结果表明,miR-9 调节 COVID-19 中的 NF-κB 信号和炎症。非幸存者中 miR-9 水平升高提示其作为严重程度生物标志物的潜力。虽然 COVID-19 病例有所减少,但靶向 miR-9 和 NF-κB 可能改善其他炎症性疾病(包括自身免疫性疾病)的结局,凸显了在该领域继续开展研究的必要性。

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