MicroRNA expression changes in lymphoblastoid cell lines in response to lithium treatment.
MicroRNA expression changes in lymphoblastoid cell lines in response to lithium treatment.
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DOI：
10.1017/s1461145709000029
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发表时间：
2009-08
期刊：
影响因子：
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通讯作者：
McInnis MG
中科院分区：
文献类型：
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作者：
Chen H;Wang N;Burmeister M;McInnis MG
锂（Li）通常用于治疗双相情感障碍（BPD）。然而，其作用的分子机制尚未完全了解。MicroRNA（miRNAs）是一类小分子RNA，是转录后基因表达的重要调控因子。为了探讨miRNA在Li作用中的作用，我们定量分析了20个淋巴母细胞样细胞系（LCL）中13种miRNA的表达模式，无论是否经过Li处理。在分析中使用配对t统计，我们鉴定了在治疗第4天取样的LCL中测试的13种miRNA中的7种的显著变化（P < 0.05）。在第16天较长的处理时间点，七种显著的miRNA中的四种，miR-34 a、miR-152、miR-155和miR-221在相同的LCL中一致地改变表达（Bonferroni P < 0.05）。有趣的是，miR-221和miR-34 a也改变了大鼠海马中的表达，以响应Li处理，尽管方向相反。我们关注miR-221和miR-34 a的预测靶mRNA，并分别鉴定了29个和10个与这两种miRNA表达强烈相关和负相关的靶。目前，我们测试了一组miRNAs，我们的结果表明，miRNAs是研究Li在细胞系统（如淋巴细胞）中治疗作用的分子基础的极好候选者，这些细胞系统被限制进入人脑。
Lithium (Li) is commonly used in the treatment of bipolar disorder (BPD). However, the molecular mechanism of its action has not completely understood. MicroRNAs (miRNAs), a class of small RNA species are recognized as important regulators in post-transcription gene expression. To explore the role of miRNA in Li action, we quantitatively analyzed the expression patterns of 13 miRNAs in 20 lymphoblastoid cell lines (LCLs) with or without Li treatment in culture. Using paired t statistics in the analysis, we identified significant changes in seven of the 13 miRNAs tested in LCLs sampled at treatment day 4 (P < 0.05). Four of the seven significant miRNAs, miR-34a, miR-152, miR-155, and miR-221 consistently changed expression in the same LCLs at a longer treatment time point day 16 (Bonferroni P < 0.05). Interestingly, miR-221 and miR-34a also changed expression in rat hippocampus in response to Li treatment, though in the opposite direction. We focused on the predicted target mRNAs of miR-221 and miR-34a, and identified 29 and ten targets that were strongly and inversely correlated in expression with the two miRNAs, respectively. At present we tested a subset of miRNAs, our results suggest that miRNAs are excellent candidates for the study of the molecular basis of Li’s treatment action in cell systems such as lymphocytes given limited access to the human brain.