Abstract
BackgroundThis study aimed to explore the correlation of circular RNA HECT domain E3 ubiquitin protein ligase 1 (circRNA HECTD1) expression with disease risk, disease severity, inflammation, and recurrence of acute ischemic stroke (AIS).MethodsA total of 160 initial AIS patients and 160 controls were enrolled in this study. Peripheral blood mononuclear cells of AIS patients and controls were separated from blood samples to detect circRNA HECTD1 expression by RT‐qPCR. Inflammatory cytokines in serum of AIS patients were measured by ELISA. Furthermore, the National Institutes of Health Stroke Scale (NIHSS) score was used to evaluate disease severity of AIS patients. Additionally, disease recurrence was documented during follow‐up, and recurrence‐free survival (RFS) was calculated.ResultsCircRNA HECTD1 expression was higher in AIS patients than that in controls, and the receiver operating characteristic (ROC) curve revealed that circRNA HECTD1 expression was of a good value in distinguishing AIS patients from controls with area under the curve (AUC) of 0.814 (95% CI: 0.768‐0.859). In AIS patients, circRNA HECTD1 expression was positively correlated with NIHSS score, CRP, and pro‐inflammatory cytokines. CircRNA HECTD1 expression was increased in AIS recurrence patients compared to non‐recurrence patients, and further, ROC curve analysis disclosed that circRNA HECTD1 expression predicted higher risk of AIS recurrence (AUC: 0.694, 95% CI: 0.586‐0.801). Additionally, circRNA HECTD1 expression was negatively correlated with RFS.ConclusionsCircRNA HECTD1 expression correlates with higher disease risk, disease severity, inflammation, and recurrence of AIS.
Highlights
Stroke is a major cause of long‐term disability and the fourth lead‐ ing cause of death worldwide.[1]
We discovered that: (a) CircRNA HECTD1 ex‐ pression was increased in acute ischemic stroke (AIS) patients compared to controls, and receiver operating characteristic (ROC) curve analysis revealed that circRNA HECTD1 expression was of a good value in distinguishing AIS patients from controls; (b) CircRNA HECTD1 expression was positively associated with National Institutes of Health Stroke Scale (NIHSS) score and inflammation in AIS patients; and (c) CircRNA HECTD1 expression predicted higher risk of AIS recurrence
Circular antisense non‐coding RNA in the INK4 locus expression is significantly higher in the whole blood from carriers of the coronary artery disease–protective haplotype compared to non‐carriers.[11]
Summary
Stroke is a major cause of long‐term disability and the fourth lead‐ ing cause of death worldwide.[1]. Circular RNAs (circRNAs), a new class of endogenous non‐cod‐ ing RNAs, are generated by back‐splicing process in eukaryotes.[5] CircRNAs form a covalently closed loop without 5′ and 3′ end, which are often expressed in tissue‐specific or disease‐specific patterns.[5,6] circRNAs are highly stable and abundant in blood; it is detected in blood samples.[5] Circular RNA HECT domain E3 ubiquitin protein ligase 1 (circRNA HECTD1) is derived from exons 23 and 24 of the HECTD1 gene.[6] Recent studies have exhibited the role of circRNA HECTD1 in the development and progression of sev‐ eral diseases such as AIS and silicosis.[7,8] For example, a study dis‐ closes that knockdown of circRNA HECTD1 attenuates infract size and decreases neurological deficits in cerebral ischemia transient middle cerebral artery occlusion mouse (tMCAO) stroke models.[7] Besides that, a preliminary study based on primary cultures of alve‐ olar macrophages from silicosis patients demonstrates that circRNA HECTD1 involves in SiO2‐mediated inflammation cascade.[8] Based on the role of circRNA HECTD1 in enlarging stroke infarct size, ac‐ celerating neurological deficits, and inflammation from previous studies, we hypothesized that circRNA HECTD1 may be involved in the development and progression of AIS. This study initially explored the correlation of circRNA HECTD1 expression with disease risk, disease severity, inflammation, and recurrence of AIS
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