Microarray profiling and co-expression network analysis of circulating lncRNAs and mRNAs associated with major depressive disorder.

Microarray profiling and co-expression network analysis of circulating lncRNAs and mRNAs associated with major depressive disorder.
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与重度抑郁症相关的循环 lncRNA 和 mRNA 的微阵列分析和共表达网络分析。

DOI:
10.1371/journal.pone.0093388
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Zhang K
Zhang K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liu Z;Li X;Sun N;Xu Y;Meng Y;Yang C;Wang Y;Zhang K

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LncRNA是脑中表达最高的一类ncRNA,在脑功能和疾病方面正变得越来越有趣。然而,在严重抑郁症(MDD)的调节lncRNA的表达的变化尚未报道。使用微阵列,我们分析了34834 lncRNA和39224 mRNA的表达在外周血样本从MDD患者以及人口统计学匹配的控制。其中,我们发现2007个lncRNA和1667个mRNAs的差异表达,其中17个在以前的研究中被证明是抑郁症相关基因。基因本体论(GO)和通路分析表明,差异表达的mRNA的生物学功能与基础代谢过程和神经发育疾病有关。为了研究差异表达的lncRNA对mRNA的潜在调控作用,我们还构建了由lncRNA和mRNA组成的共表达网络,该网络显示出显著相关的表达模式。在MDD衍生网络中,有更多的节点和连接比在控制衍生网络。位于chr 10:874695-874794、chr 10:75873456-75873642和chr 3:47048304-47048512的lncRNA可能是调节mRNA表达的重要因素,因为它们先前已被报道与MDD相关。这项研究是第一个探索全基因组lncRNA表达和共表达与mRNA模式在MDD使用微阵列技术。我们鉴定了MDD中异常表达的循环lncRNA,结果表明lncRNA可能有助于MDD的分子发病机制。
LncRNAs, which represent one of the most highly expressed classes of ncRNAs in the brain, are becoming increasingly interesting with regard to brain functions and disorders. However, changes in the expression of regulatory lncRNAs in Major Depressive Disorder (MDD) have not yet been reported. Using microarrays, we profiled the expression of 34834 lncRNAs and 39224 mRNAs in peripheral blood sampled from MDD patients as well as demographically-matched controls. Among these, we found that 2007 lncRNAs and 1667 mRNAs were differentially expressed, 17 of which were documented as depression-related gene in previous studies. Gene Ontology (GO) and pathway analyses indicated that the biological functions of differentially expressed mRNAs were related to fundamental metabolic processes and neurodevelopment diseases. To investigate the potential regulatory roles of the differentially expressed lncRNAs on the mRNAs, we also constructed co-expression networks composed of the lncRNAs and mRNAs, which shows significant correlated patterns of expression. In the MDD-derived network, there were a greater number of nodes and connections than that in the control-derived network. The lncRNAs located at chr10:874695-874794, chr10:75873456-75873642, and chr3:47048304-47048512 may be important factors regulating the expression of mRNAs as they have previously been reported associations with MDD. This study is the first to explore genome-wide lncRNA expression and co-expression with mRNA patterns in MDD using microarray technology. We identified circulating lncRNAs that are aberrantly expressed in MDD and the results suggest that lncRNAs may contribute to the molecular pathogenesis of MDD.
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