Zhang Shuai, Wang Jing, Qu Mei Jie, Wang Kun, Ma Ai Jun, Pan Xu Dong, Zhu Xiao Yan
Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Institute of Cerebrovascular Diseases, The Affiliated Hospital of Qingdao University, Qingdao, China.
Front Mol Biosci. 2021 May 21;8:682769. doi: 10.3389/fmolb.2021.682769. eCollection 2021.
Exosomes show diagnostic and therapeutic promise as carriers of ncRNAs in diseases. LncRNAs in exosomes have been identified as being stable and avoided degradation by nucleolytic enzymes. Although lncRNAs have been confirmed to be important in cancers, no studies for exo-lncRNAs have been reported in LAA stroke. High-throughput sequencing was performed to detect the differential expression profiles of lncRNAs in five paired plasma-derived exosome samples from patients with LAA stroke and controls (matched on vascular risk factors). Exo-lncRNA-associated networks were predicted with a combination of multiple databases. The expression of the selected genes in the networks was confirmed by qRT-PCR in a validation set (LAA vs. controls = 30:30). Furthermore, ROC analysis was used to evaluate the diagnostic performance of the lncRNA-related networks. A total of 1,020 differentially expressed lncRNAs were identified in LAA stroke patients. GO and KEGG pathway analyses indicated that their target genes are involved in atherosclerosis-related pathways, including inflammation, cell adhesion, and cell migration. qRT-PCR confirmed that the expression trend of differential expressed genes was consistent with RNA-seq. Furthermore, the AUCs of the lnc_002015-related network and lnc_001350-related network were 0.959 and 0.97, respectively, in LAA stroke. Our study showed the differential expression of lncRNAs in plasma exosomes and presented related diagnostic networks for LAA stroke for the first time. The results suggested that exosomal lncRNA-related networks could be potential diagnostic tools in LAA stroke.
外泌体作为疾病中ncRNAs的载体显示出诊断和治疗前景。外泌体中的lncRNAs已被确定为稳定的，并且能够避免被核酸酶降解。尽管lncRNAs已被证实在癌症中很重要，但在大动脉粥样硬化性（LAA）卒中中尚未有关于外泌体lncRNAs的研究报道。对来自LAA卒中患者和对照组（在血管危险因素方面匹配）的五对血浆来源的外泌体样本进行高通量测序，以检测lncRNAs的差异表达谱。结合多个数据库预测外泌体lncRNA相关网络。通过qRT-PCR在验证集（LAA组与对照组=30:30）中确认网络中所选基因的表达。此外，使用ROC分析评估lncRNA相关网络的诊断性能。在LAA卒中患者中总共鉴定出1020个差异表达的lncRNAs。GO和KEGG通路分析表明它们的靶基因参与了与动脉粥样硬化相关的通路，包括炎症、细胞粘附和细胞迁移。qRT-PCR证实差异表达基因的表达趋势与RNA测序一致。此外，在LAA卒中中，lnc_002015相关网络和lnc_001350相关网络的AUC分别为0.959和0.97。我们的研究首次显示了血浆外泌体中lncRNAs的差异表达，并呈现了LAA卒中的相关诊断网络。结果表明，外泌体lncRNA相关网络可能是LAA卒中的潜在诊断工具。
