Circulating lncRNAs HIF1A-AS2 and LINLK-A: Role and Relation to Hypoxia-Inducible Factor-1α in Cerebral Stroke Patients

Abstract

Long noncoding RNAs (lncRNAs) have been recently recognized as key players of gene expression in cerebral pathogenesis. Thus, their potential use in stroke diagnosis, prognosis and therapy is actively pursued. Due to the complexity of the disease, identifying stroke-speci c lncRNAs remains a challenge.This study investigated the expression of lncRNAs; HIF1A-AS2 and LINK-A and their target gene Hypoxiainducible factor-1 (HIF-1) in Egyptian stroke patients. It also aimed to determine the molecular mechanism implicated in the disease. A total of 75 stroke patients were divided into three clinical subgroups, beside 25 healthy controls of matched age and sex. Remarkable upregulation of lncRNA HIF1A-AS2 and HIF1-α along with a downregulation of lncRNA LINK-A were noticed in all stroke groups relative to controls. Serum levels of phosphatidylinositol 3-kinase (PI3K), phosphorylated-Akt (p-Akt), vascular endothelial growth factor (VEGF) and angiopoietin-1 (ANG1) as well as their receptors, malondialdehyde (MDA) and total antioxidant capacity (TAC) were signi cantly increased, whereas brainderived neurotrophic factor (BDNF) levels were signi cantly decreased particularly in hemorrhagic stroke versus ischemic groups. Eventually, these ndings support the role of lncRNAs; HIF1A-AS2 and LINK-A as well as HIF1-α in activation of angiogenesis, neovascularization, and better prognosis of stroke, especially the hemorrhagic type. Introduction:Cerebral stroke is a major health problem affecting a large population in both developed and developing countries [1]. Without rapid successful intervention, stroke can cause sudden cerebral death or severe prolonged disability [1]. Two main types of stroke are identi ed: ischemic stroke (thrombotic and embolic) and hemorrhagic stroke (cerebral and subarachnoid). Although hemorrhagic stroke is much more fatal, prevalence and incidence rates of thrombotic showed the highest ones, followed by cerebral hemorrhage, then embolic and lastly subarachnoid hemorrhage [2]. Among the di culties for timely treatment and management of stroke are the complexity of the disease resulting from its multiple underlying risk factors, lack of sensitive and speci c biomarkers for easily diagnosis and prognosis as well as potential therapy. Therefore, the need for more reliable biomarkers is highly desired. It is known that apparent changes in the expression of multiple genes in cerebrum are a major cause as well as useful predictors of the pathogenesis in cerebral stroke. Identi cation of such genes, particularly those that are highly speci c and sensitive to stroke may be the key step towards reliable prediction of stroke. Hence, enhanced understanding of stroke pathogenesis would aid in the early detection and optimal disease management.In stroke, large sequence of biochemical and molecular pathways, causing neuron cell death, were previously linked to the imbalance between oxygen supply and demand in the cerebral tissue. Hypoxic conditions, associated with cerebrovascular stroke, are a strong challenge for oxyg...

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“…The RT reaction was incubated for 60 min at 37 °C, followed by 5 min at 95 °C. The produced cDNA was kept at −20 °C until analysis was conducted [ 22 , 38 ].…”

“…The reaction was performed with a PCR initial activation at 95 °C for 15 min followed by 40 cycles at 95 °C for 15 s, 55 °C for 30 s, and 72 °C for 30 s. Data were analyzed with Rotor Gene Q software (Qiagen, Germany) with the automatic threshold cycle (Ct) setting. Then the relative expression for each measured biomarker after normalization to GAPDH as an endogenous control was calculated by applying the 2 −ΔΔct method and presented as fold change [ 22 , 38 ].…”

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