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首页> 美国卫生研究院文献>International Journal of Molecular Sciences >Whole Genome Expression Analyses of miRNAs and mRNAs Suggest the Involvement of miR-320a and miR-155-3p and their Targeted Genes in Lithium Response in Bipolar Disorder
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Whole Genome Expression Analyses of miRNAs and mRNAs Suggest the Involvement of miR-320a and miR-155-3p and their Targeted Genes in Lithium Response in Bipolar Disorder

机译：miRNA和mRNA的全基因组表达分析表明miR-320a和miR-155-3p及其靶基因参与双相性精神障碍锂反应。

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Lithium is the mainstay in the maintenance of bipolar disorder (BD) and the most efficacious pharmacological treatment in suicide prevention. Nevertheless, its use is hampered by a high interindividual variability and important side effects. Genetic and epigenetic factors have been suggested to modulate lithium response, but findings so far have not allowed identifying molecular targets with predictive value. In this study we used next generation sequencing to measure genome-wide miRNA expression in lymphoblastoid cell lines from BD patients excellent responders (ER, = 12) and non-responders (NR, = 12) to lithium. These data were integrated with microarray genome-wide expression data to identify pairs of miRNA/mRNA inversely and significantly correlated. Significant pairs were prioritized based on strength of association and in-silico miRNA target prediction analyses to select candidates for validation with qRT-PCR. Thirty-one miRNAs were differentially expressed in ER vs. NR and inversely correlated with 418 genes differentially expressed between the two groups. A total of 331 of these correlations were also predicted by in-silico algorithms. miR-320a and miR-155-3p, as well as three of their targeted genes ( (Calpain Small Subunit 1) and (Regulator of G Protein Signaling 16) for miR-320, (Sp4 Transcription Factor) for miR-155-3p) were validated. These miRNAs and mRNAs were previously implicated in psychiatric disorders (miR-320a and ), key processes of the central nervous system ( , , ) or pathways involved in mental illnesses (miR-155-3p). Using an integrated approach, we identified miRNAs and their targeted genes potentially involved in lithium response in BD.
机译：锂是维持双相情感障碍（BD）的主要手段，也是预防自杀最有效的药物治疗方法。然而，其使用因个体之间的高度变异性和重要的副作用而受到阻碍。遗传和表观遗传因素已被建议调节锂反应，但迄今为止的发现尚未允许鉴定具有预测价值的分子靶标。在这项研究中，我们使用了下一代测序技术来测量BD患者对锂的优秀反应者（ER，= 12）和无反应者（NR，= 12）的淋巴母细胞细胞系中的全基因组miRNA表达。将这些数据与微阵列全基因组表达数据整合在一起，以反向和显着相关地鉴定成对的miRNA / mRNA。根据关联强度和计算机内miRNA靶标预测分析，对重要的配对进行优先级排序，以选择可用于qRT-PCR验证的候选物。在ER与NR中差异表达了31个miRNA，并且与两组之间差异表达的418个基因负相关。通过计算机内算法也预测了其中的331种相关性。 miR-320a和miR-155-3p，以及它们的三个靶基因（miR-320的（钙蛋白酶小亚基1）和G蛋白信号调节因子16），miR-155-3p的（Sp4转录因子） ）进行了验证。这些miRNA和mRNA先前与精神疾病（miR-320a和），中枢神经系统的关键过程（，）或涉及精神疾病的途径（miR-155-3p）有关。使用整合的方法，我们确定了可能与BD锂反应有关的miRNA及其靶向基因。

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