Altered lncRNAs Transcriptomic Profiles in Atherosclerosis-Induced Ischemic Stroke
Altered lncRNAs Transcriptomic Profiles in Atherosclerosis-Induced Ischemic Stroke
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DOI：
10.1007/s10571-020-00918-y
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发表时间：
2020-07
影响因子：
4
通讯作者：
Wenchen Ruan;Jiayang Wu;Jingjing Su;Yongcheng Jiang;Tao Pang;Jingwei Li
中科院分区：
文献类型：
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作者：
Wenchen Ruan;Jiayang Wu;Jingjing Su;Yongcheng Jiang;Tao Pang;Jingwei Li
长链非编码RNA（lncRNA）不仅可以调控基因的转录和翻译，还可以作为表观遗传修饰因子参与中枢神经系统疾病的发生发展。然而，其在动脉粥样硬化诱导的缺血性卒中（AIIS）中的功能意义尚不清楚。本研究旨在筛选差异表达的lncRNA（delncRNA），并阐明其在AIIS病理生理中的潜在调控机制。根据临床病理特征和临床影像学资料，筛选出10例AIIS患者，并招募10名健康志愿者。然后利用基因芯片检测受试者全血RNA，通过GO和KEGG分析探讨delncRNA的生物学功能。在进一步分析ox-LDL刺激THP-1的delncRNA后，通过共表达分析筛选出选择性lncRNA，并构建了相应的lncRNA-mRNA相互作用网络。我们得到了180个delncRNA（44个上调和136个下调）和218个demRNA（45个上调和173个下调）。lnc-SCARNA 8和lnc-SNRPN-2分别是AIIS中最显著升高和降低的lncRNA。delncRNA可能在遍在化介导的蛋白质降解信号通路中发挥重要作用。根据lncRNA-mRNA网络，液泡蛋白分选13同源物B（VPS13 B）和胆绿素还原酶B（BLVRB）的表达受到显著调节。我们的研究结果表明，泛素化蛋白酶体途径，VPS13 B和BLVRB可能在AIIS的病理过程中发挥了重要作用。
Long non-coding RNAs (lncRNAs) can not only regulate gene transcription and translation, but also participate in the development of central nervous system diseases as epigenetic modification factors. However, their functional significance in atherosclerosis-induced ischemic stroke (AIIS) is unclear. The study aimed to screen out differentially expressed lncRNAs (delncRNAs), and to elucidate their potential regulatory mechanisms in the pathophysiology of AIIS. Based on the clinicopathological features and clinical images, we screened out 10 patients with AIIS and recruited 10 healthy volunteers. Then we used microarray to detect the whole blood RNA of subjects, and explored the biological functions of delncRNAs by GO and KEGG analysis. After further analyzing the delncRNAs of THP-1 stimulated with ox-LDL, selective lncRNAs were screened and a corresponding lncRNA–mRNA interaction network was constructed through co-expression analysis. We yielded 180 delncRNAs (44 up-regulated and 136 down-regulated) and 218 demRNAs (45 up-regulated and 173 down-regulated). Lnc-SCARNA8 and lnc-SNRPN-2 are the most significant elevated and decreased lncRNA in AIIS, respectively. The delncRNAs may play a significant role in ubiquitination-mediated protein degradation signaling pathways. According to lncRNA–mRNA network, the expression of vacuolar protein sorting 13 homolog B (VPS13B) and biliverdin reductase B (BLVRB) were significantly regulated. Our findings suggest that the ubiquitinated proteasome pathway, VPS13B and BLVRB may play a fundamental role in the pathological process of AIIS.