Identification of Novel LncRNA Biomarkers and Construction of LncRNA-Related Networks in Han Chinese Patients with Ischemic Stroke
Identification of Novel LncRNA Biomarkers and Construction of LncRNA-Related Networks in Han Chinese Patients with Ischemic Stroke
复制标题
中国汉族缺血性脑卒中患者新型 LncRNA 生物标志物的鉴定及 LncRNA 相关网络的构建
DOI：
10.1159/000495058
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Su, Li
中科院分区：
文献类型：
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作者：
Guo, Xiaojing;Yang, Jialei;Su, Li
背景/目标：长链非编码RNA（longnoncodingRNA，lncRNA）由于与编码RNA相互作用，成为肿瘤、心脏病和脑疾病的潜在生物标志物。本研究以缺血性脑卒中（ischemic stroke，IS）为研究对象，旨在鉴定新的lncRNA生物标志物，构建IS中lncRNA相关网络。方法：采用Arraystar Human LncRNA Microarray v4.0鉴定差异表达的lncRNA，qRT-PCR验证差异表达的lncRNA。构建了lncRNA-mRNA共表达网络和lncRNA-miRNA-mRNA调控网络。然后进行功能和途径分析。结果如下：共发现560个上调和690个下调的差异表达lncRNA（P < 0.05，假发现率< 0.05，绝对倍数变化≥ 2）。qRT-PCR结果证实lncRNA-ENST 00000568297、lncRNA-ENST 00000568243和lncRNA-NR_046084在IS和对照之间表现出显著差异表达（均P < 0.05）。这些lncRNA的曲线下面积（AUC）分别为0.733、0.743和0.690，合并的AUC为0.843。基于Pearson相关系数构建编码-非编码共表达网络。还构建了ENST 00000568297、ENST 00000568243和NR_046084的特异性lncRNA-miRNA-mRNA调控网络。进行上调和下调mRNA的功能注释。通路分析丰富了lncRNA-miRNA-mRNA调控网络中mRNA的IS相关通路。结论：IS后人外周血LncRNA和mRNA表达谱发生改变。ENST 00000568297、ENST 00000568243和NR_046084被确定为IS的新型潜在诊断生物标志物。CNC网络和lncRNA-miRNA-mRNA调控网络的分析表明，lncRNA可能通过调节关键的miRNA、mRNA或IS相关通路参与IS病理生理学。
Background/Aims: Long non-coding RNAs (lncRNAs) are potential biomarkers of tumors, cardiac disease, and cerebral disease because of their interaction with coding RNAs. This work focused on ischemic stroke (IS) and aimed to identify novel lncRNA biomarkers and construct lncRNA-related networks in IS. Methods: Differentially expressed lncRNAs were identified using Arraystar Human LncRNA Microarray v4.0, and validated with qRT-PCR. A lncRNA–mRNA co-expression network and a lncRNA–miRNA–mRNA regulatory network were constructed. Functional and pathway analyses were then performed. Results: In total, 560 up-regulated and 690 down-regulated differentially expressed lncRNAs were found (P < 0.05, false discovery rate < 0.05, absolute fold change ≥ 2). qRT-PCR results confirmed that lncRNA-ENST00000568297, lncRNA-ENST00000568243, and lncRNA-NR_046084 exhibited significant differential expression between IS and controls (all P < 0.05). Areas under the curves (AUCs) for these lncRNAs were 0.733, 0.743, and 0.690, respectively, and the combined AUC was 0.843. A coding–noncoding co-expression (CNC) network was constructed based on Pearson’s correlation coefficient. A specific lncRNA–miRNA–mRNA regulatory network of ENST00000568297, ENST00000568243, and NR_046084 was also constructed. Functional annotation of the up- and down-regulated mRNAs was performed. Pathway analysis enriched IS-related pathways with mRNAs in the lncRNA–miRNA–mRNA regulatory network. Conclusion: LncRNA and mRNA expression profiles in human peripheral blood were altered after IS. ENST00000568297, ENST00000568243, and NR_046084 were identified as novel potential diagnostic biomarkers of IS. Analysis of the CNC network and lncRNA–miRNA–mRNA regulatory network suggested that lncRNAs may participate in IS pathophysiology by regulating pivotal miRNAs, mRNAs, or IS-related pathways.