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

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.