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

Abstract

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\u2009<\u20090.01). NR_028138.1 was used to establish a BD diagnostic model (area under the ROC curve 0.923, P\u2009<\u20090.004, 95% CI: 0.830–0.999). Verification in the second cohort revealed uniformly significant differences in NR_028138.1 (P\u2009<\u20090.0001). 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.