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动脉粥样硬化性缺血性卒中中lncRNAs转录组图谱的改变

Altered lncRNAs Transcriptomic Profiles in Atherosclerosis-Induced Ischemic Stroke.

作者信息

Ruan Wenchen, Wu Jiayang, Su Jingjing, Jiang Yongcheng, Pang Tao, Li Jingwei

机构信息

Department of Neurology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, People's Republic of China.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, #24 Tong Jia Xiang Street, Nanjing, 210009, People's Republic of China.

出版信息

Cell Mol Neurobiol. 2022 Jan;42(1):265-278. doi: 10.1007/s10571-020-00918-y. Epub 2020 Jul 11.

Abstract

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.

摘要

长链非编码RNA(lncRNAs)不仅可以调节基因转录和翻译,还可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,它们在动脉粥样硬化性缺血性卒中(AIIS)中的功能意义尚不清楚。本研究旨在筛选出差异表达的lncRNAs(delncRNAs),并阐明其在AIIS病理生理学中的潜在调控机制。基于临床病理特征和临床影像,我们筛选出10例AIIS患者,并招募了10名健康志愿者。然后我们使用微阵列检测受试者的全血RNA,并通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析探索delncRNAs的生物学功能。在进一步分析经氧化型低密度脂蛋白(ox-LDL)刺激的人单核细胞白血病细胞株(THP-1)的delncRNAs后,筛选出选择性lncRNAs,并通过共表达分析构建相应的lncRNA-信使核糖核酸(mRNA)相互作用网络。我们得到了180个delncRNAs(44个上调和136个下调)和218个差异表达的mRNA(demRNAs,45个上调和173个下调)。Lnc-SCARNA8和lnc-SNRPN-2分别是AIIS中上调和下调最显著的lncRNA。这些delncRNAs可能在泛素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(VPS13B)和胆绿素还原酶B(BLVRB)的表达受到显著调控。我们的研究结果表明,泛素化蛋白酶体途径、VPS-13B和BLVRB可能在AIIS的病理过程中起重要作用。

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