Department of Cardiovascular Medicine, Second Affiliated Hospital of Nanchang University, Minde Road No. 1, Nanchang, 330006, Jiangxi, China.
Department of Clinical Laboratory, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
Sci Rep. 2021 Aug 2;11(1):15653. doi: 10.1038/s41598-021-94122-7.
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.
双相情感障碍(BD)是一种慢性情绪障碍,其发病机制在很大程度上尚不清楚。非编码 RNA 在 BD 的发病机制中发挥重要作用。然而,关于长非编码 RNA(lncRNA)与 BD 的相关性知之甚少。使用 Illumina 高通量测序在 BD 患者和正常对照中识别差异表达(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 名 BD 和 50 名对照)中的 DE-RNAs。基因本体论(GO)和京都基因与基因组百科全书(KEGG)途径以及 lncRNA-mRNA 共表达和 lncRNA-miRNA-信使 RNA(mRNA)竞争内源性 RNA(ceRNA)网络分析用于预测 DE-RNAs 的功能。接收器操作特征(ROC)曲线分析和逻辑回归用于评估另外一组(80 名 BD 和 66 名对照)的诊断性能。在 BD 患者中鉴定出 576 个显着差异表达的 lncRNA 和 262 个差异表达的 mRNA,使用 95 个 lncRNA-miRNA-mRNA 相互作用构建 ceRNA 调控网络。对第一队列的分析表明,BD 组有 6 个 RNA(NR_028138.1、TCONS_00018621、TCONS_00002186、TNF、PID1 和 SDK1)表达差异(P < 0.01)。NR_028138.1 用于建立 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 存在显着差异(P < 0.0001)。本研究构建了 ceRNA 调控网络,为 BD 的发病机制提供了假说。NR_028138.1 被确定为 BD 中参与转录调控的核心元件,是一种潜在的生物标志物。