Identification of lncRNA NR_028138.1 as a biomarker and construction of a ceRNA network for bipolar disorder.

Identification of lncRNA NR_028138.1 as a biomarker and construction of a ceRNA network for bipolar disorder.
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DOI:
10.1038/s41598-021-94122-7
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发表时间:
2021-08-02
期刊:
影响因子:
4.6
通讯作者:
Li J
Li J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
He L;Zou P;Sun W;Fu Y;He W;Li J

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双相情感障碍(BD)是一种慢性心境障碍,其发病机制尚不清楚。非编码RNA在BD的发病机制中起重要作用。然而,很少有人知道长链非编码RNA(lncRNA)与BD的相关性。BD患者和正常对照的Illumina高通量测序用于鉴定差异表达(DE)基因。两步实时定量逆转录聚合酶链反应(qRT-PCR)用于验证第一队列(50例BD受试者和50例对照受试者)中的DE-RNA。利用GO和KEGG途径以及lncRNA-mRNA共表达和lncRNA-microRNA(miRNA)-信使RNA(mRNA)竞争性内源RNA(ceRNA)网络分析预测DE-RNA的功能。应用受试者工作特征(ROC)曲线分析和逻辑回归来评估额外测试组(80例BD和66例对照受试者)的诊断性能。在BD患者中共鉴定出576个显著DE-lncRNA和262个DE-mRNA,并使用95个lncRNA-miRNA-mRNA相互作用来构建ceRNA调控网络。对第一组的分析显示,6种RNA(NR_028138.1、TCONS_00018621、TCONS_00002186、TNF、PID1和SDK1)在BD组中差异表达(P <0.01)。采用NR_028138.1建立BD诊断模型(ROC曲线下面积0.923,P <0.004,95%CI:0.830 - 0.999)。在第二队列中的验证显示NR_028138.1的一致显著差异(P <0.0001)。本研究构建了一个ceRNA调控网络,为BD的发病机制提供了假说。NR_028138.1被鉴定为参与BD转录调控的中心元件和潜在的生物标志物。
The pathogenesis of bipolar disorder (BD), a chronic mood disorder, is largely unknown. Noncoding RNAs play important roles in the pathogenesis of BD. However, little is known about the correlations of long noncoding RNAs (lncRNAs) with BD. Illumina high-throughput sequencing in BD patients and normal controls was used to identify differentially expressed (DE) genes. Two-step real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate DE-RNAs in the first cohort (50 BD and 50 control subjects). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and lncRNA-mRNA coexpression and lncRNA-microRNA (miRNA)-messenger RNA (mRNA) competing endogenous RNA (ceRNA) network analyses were used to predict the functions of DE-RNAs. Receiver operating characteristic (ROC) curve analysis and logistic regression were applied to evaluate diagnostic performance in an additional testing group (80 BD and 66 control subjects). A total of 576 significantly DE-lncRNAs and 262 DE-mRNAs were identified in BD patients, and 95 lncRNA-miRNA-mRNA interactions were used to construct a ceRNA regulatory network. Analysis of the first cohort showed that six RNAs (NR_028138.1, TCONS_00018621, TCONS_00002186, TNF, PID1, and SDK1) were differentially expressed in the BD group (P < 0.01). NR_028138.1 was used to establish a BD diagnostic model (area under the ROC curve 0.923, P < 0.004, 95% CI: 0.830–0.999). Verification in the second cohort revealed uniformly significant differences in NR_028138.1 (P < 0.0001). This study constructed a ceRNA regulatory network and provided a hypothesis for the pathogenesis of BD. NR_028138.1 was identified as a central element involved in the transcriptional regulation in BD and a potential biomarker.
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