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长链非编码RNA XIST/微小RNA-340-5p轴及代谢重编程生物标志物在急性脑血管卒中患者中的表达及意义:一项横断面研究

The expression and significance of long noncoding RNA XIST/microRNA-340-5p axis and metabolic reprogramming biomarkers in acute cerebrovascular stroke patients: A cross-sectional study.

作者信息

Elhorany Mahmoud, El-Horany Hemat E, Abd-Ellatif Rania Nagi, Dawood Lamees M, Watany Mona M, Basiouny Mohamed Abdelaziz, Hegab Islam Ibrahim, Alsheikh Mona Y, Kabel Ahmed M, Atef Marwa M

机构信息

Neuropsychiatry Department, Faculty of Medicine, Tanta University, Tanta, Egypt.

Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta, Egypt.

出版信息

Medicine (Baltimore). 2024 Dec 27;103(52):e41092. doi: 10.1097/MD.0000000000041092.

Abstract

Stroke represents a worldwide major cause of death and long-term adult disability. Various human diseases pathogenesis, including stroke, are associated with dysregulation of long noncoding RNA (LncRNA) and microRNA (miR). However, their potential role is yet to be elucidated. This work aimed to assess the role of LncRNA X-inactive specific transcript (XIST), miR-340-5p, and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB)3 as peripheral blood biomarkers for acute cerebrovascular stroke diagnosis and severity prediction. This cross-sectional study included 120 participants divided into 3 groups; healthy controls, acute ischemic stroke patients, and acute hemorrhagic stroke patients. XIST, miR-340-5p, and PFKFB3 expression were assessed by RT-qPCR, whereas PFKFB3, hypoxia inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF) serum proteins were measured by ELISA. Compared to healthy control, XIST and PFKFB3 mRNA expression were significantly upregulated in stroke patients, with the highest levels in hemorrhagic type, while miR-340-5p expression was significantly downregulated and its lowest level was in hemorrhagic stroke. Serum PFKFB3, HIF-1α, and VEGF levels were significantly elevated in stroke patients with the highest levels in hemorrhagic stroke. These biomarkers correlated with National Institute of Health Stroke Scale (NIHSS). Regression analysis using NIHSS as dependent variable confirmed that PFKFB3 mRNA relative expression was the independent predictor (β = 0.7, P = .003). Receiver operating characteristic analyses revealed that XIST, miR-340-5p, and PFKFB3 mRNA relative expression levels were useful biomarkers discriminating ischemic from hemorrhagic stroke (AUC were 0.99, 0.979, and 0.980, respectively). XIST, miR-340-5p, and PFKFB3 might be involved in acute cerebrovascular stroke pathogenesis and progression providing opportunities for early detection and assessing the severity.

摘要

中风是全球范围内主要的死亡原因和成人长期残疾的原因。包括中风在内的各种人类疾病的发病机制都与长链非编码RNA(LncRNA)和微小RNA(miR)的失调有关。然而,它们的潜在作用尚待阐明。这项研究旨在评估LncRNA X染色体失活特异性转录本(XIST)、miR-340-5p和6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶(PFKFB)3作为外周血生物标志物在急性脑血管中风诊断和严重程度预测中的作用。这项横断面研究纳入了120名参与者,分为3组:健康对照组、急性缺血性中风患者和急性出血性中风患者。通过RT-qPCR评估XIST、miR-340-5p和PFKFB3的表达,而通过ELISA测量PFKFB3、缺氧诱导因子1-α(HIF-1α)和血管内皮生长因子(VEGF)的血清蛋白。与健康对照组相比,中风患者中XIST和PFKFB3 mRNA表达显著上调,出血型患者中表达水平最高,而miR-340-5p表达显著下调,其最低水平出现在出血性中风患者中。中风患者血清PFKFB3、HIF-1α和VEGF水平显著升高,出血性中风患者中水平最高。这些生物标志物与美国国立卫生研究院卒中量表(NIHSS)相关。以NIHSS为因变量的回归分析证实,PFKFB3 mRNA相对表达是独立预测因子(β = 0.7,P = 0.003)。受试者工作特征分析显示,XIST、miR-340-5p和PFKFB3 mRNA相对表达水平是区分缺血性中风和出血性中风的有用生物标志物(AUC分别为0.99、0.979和0.980)。XIST、miR-340-5p和PFKFB3可能参与急性脑血管中风的发病机制和进展,为早期检测和评估严重程度提供了机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed43/11688033/efdb66479725/medi-103-e41092-g001.jpg

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