Altered expression of long noncoding RNAs in peripheral blood mononuclear cells in patients with impaired leptomeningeal collaterals after acute anterior large vessel occlusions

Altered expression of long noncoding RNAs in peripheral blood mononuclear cells in patients with impaired leptomeningeal collaterals after acute anterior large vessel occlusions
复制标题

急性前大血管闭塞后软脑膜侧枝受损患者外周血单核细胞中长非编码RNA表达的改变

DOI:
10.21037/atm.2019.10.02
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发表时间:
2019-10-01
影响因子:
--
通讯作者:
Qin, Xinyue
Qin, Xinyue
中科院分区:
医学4区
文献类型:
--
作者:
Wu, Qisi;Le, Ting;Qin, Xinyue

文献摘要

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Background: In the event of acute ischemic stroke (AIS) due to anterior large vessel occlusion (aLVO), leptomeningeal collaterals (LMCs) status is a key factor to define the severity and functional prognosis of this disease. However, the extent of LMCs exhibits substantial variability among the patients, which is genetic determined. Long non-coding RNAs (lncRNAs) expression profiles in human peripheral blood have been found to be altered after MS. But whether there are specific lncRNAs correlated with LMC status in aLVO has not yet been investigated.Methods: Differential lncRNA expression panels in peripheral blood mononuclear cells (PBMCs) were assessed by microarray analysis and individual quantitative real-time polymerase chain reaction (RT-PCR) in three independent sets consist of 134 patients with aLVO and 73 healthy controls (HCs). LA/IQ Status in those patients was assessed based on baseline computed tomographic angiography (CTA).Results: Microarray analysis showed 23 differentially expressed lncRNAs in patients with poor LMCs status. After independent validations by RT-PCR, lncRNA ENST00000422956 was found to be significantly downregulated in patients with poor LMCs status. Receiver-operating characteristic (ROC) analysis revealed the area under the ROC curve (AUC) for ENST00000422956 to predict poor LMCs status was 0.749. Moreover, ENST00000422956 expression level and baseline National Institutes of Health Stroke Scale (NIHSS) score were identified as independent predictors for impaired LMCs, and a significantly positive correlation was observed between ENST(XX)(X)422956 expression level and LMCs status. Via cis-regulatory analysis, paired box 8 (Pax8) was identified as the target gene for ENST00000422956.Conclusions: The dysregulated lncRNA ENST00000422956 in PBMCs was associated with impairment of LMCs in patients with aLVO, suggesting that measurement of circulatory lncRNAs might be included as possible biomarkers for evaluation of LMCs status in MS. More importantly, this might be the foundation for understand the potential roles of lncRNAs in LMCs formation after ischemic stroke.