Zou Zhi-Li, Ye Yu, Zhou Bo, Zhang Yuan
Department of Psychosomatic, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Chengdu 610072, Sichuan Province, China.
Sichuan Provincial Center for Mental Health, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu 611130, Sichuan Province, China.
World J Psychiatry. 2023 Feb 19;13(2):36-49. doi: 10.5498/wjp.v13.i2.36.
Major depressive disorder (MDD) is a common and serious mental illness. Many novel genes in MDD have been characterized by high-throughput methods such as microarrays or sequencing. Recently, noncoding RNAs (ncRNAs) were suggested to be involved in the complicated environmental-genetic regulatory network of MDD occurrence; however, the interplay among RNA species, including protein-coding RNAs and ncRNAs, in MDD remains unclear.
To investigate the RNA expression datasets downloaded from a public database and construct a network based on differentially expressed long noncoding RNA (lncRNAs), microRNAs (miRNAs), and mRNAs between MDD and controls.
Gene expression data were searched in NCBI Gene Expression Omnibus using the search term "major depressive disorder." Six array datasets from humans were related to the search term: GSE19738, GSE32280, GSE38206, GSE52790, GSE76826, and GSE81152. These datasets were processed for initial assessment and subjected to quality control and differential expression analysis. Differentially expressed lncRNAs, miRNAs, and mRNAs were determined, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed, and protein-protein interaction network was generated. The results were analyzed for their association with MDD.
After analysis, 3 miRNAs, 12 lncRNAs, and 33 mRNAs were identified in the competing endogenous RNA network. Two of these miRNAs were earlier shown to be involved in psychiatric disorders, and differentially expressed mRNAs were found to be highly enriched in pathways related to neurogenesis and neuroplasticity as per Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The expression of hub gene fatty acid 2-hydroxylase was enriched, and the encoded protein was found to be involved in myelin formation, indicating that neurological development and signal transduction are involved in MDD pathogenesis.
The present study presents candidate ncRNAs involved in the neurogenesis and neuroplasticity pathways related to MDD.
重度抑郁症（MDD）是一种常见且严重的精神疾病。许多MDD中的新基因已通过微阵列或测序等高通量方法得以表征。最近，非编码RNA（ncRNA）被认为参与了MDD发生的复杂环境-基因调控网络；然而，包括蛋白质编码RNA和ncRNA在内的RNA种类之间在MDD中的相互作用仍不清楚。
研究从公共数据库下载的RNA表达数据集，并基于MDD患者与对照之间差异表达的长链非编码RNA（lncRNA）、微小RNA（miRNA）和信使RNA（mRNA）构建一个网络。
在NCBI基因表达综合数据库中使用搜索词“重度抑郁症”搜索基因表达数据。来自人类的六个阵列数据集与该搜索词相关：GSE19738、GSE32280、GSE38206、GSE52790、GSE76826和GSE81152。对这些数据集进行初步评估处理，并进行质量控制和差异表达分析。确定差异表达的lncRNA、miRNA和mRNA，进行基因本体论和京都基因与基因组百科全书富集分析，并生成蛋白质-蛋白质相互作用网络。分析结果与MDD的相关性。
经过分析，在竞争性内源RNA网络中鉴定出3种miRNA、12种lncRNA和33种mRNA。其中两种miRNA先前已被证明与精神疾病有关，根据基因本体论和京都基因与基因组百科全书富集分析，发现差异表达的mRNA在与神经发生和神经可塑性相关的途径中高度富集。枢纽基因脂肪酸2-羟化酶的表达得到富集，并且发现其编码的蛋白质参与髓鞘形成，表明神经发育和信号转导参与了MDD的发病机制。
本研究提出了参与与MDD相关的神经发生和神经可塑性途径的候选ncRNA。
