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首页> 外文期刊>The Journal of toxicological sciences >Microarray analysis of 6-mercaptopurine-induced-toxicity-related genes and microRNAs in the rat placenta
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Microarray analysis of 6-mercaptopurine-induced-toxicity-related genes and microRNAs in the rat placenta

机译：大鼠胎盘中6-巯基嘌呤诱导毒性相关基因和微瘤的微阵列分析

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MicroRNAs (miRNAs) are small single-stranded RNAs of 19-25 nucleotides and are important in posttranscriptional regulation of genes. Recently, the role of miRNAs in toxicity incidence is reported to be a regulator of key-stopper of gene expression, however the detailed mechanism of miRNAs is not well known yet. 6-Mercaptopurine (6-MP), the anti-leukemic and immunosuppressive drug, produced teratogenicity and pregnancy loss. We focused on the placenta to evaluate toxicity in embryo/fetal development produced by 6-MP treatment. MiRNA expression in the placenta was analyzed by miRNA microarray. Fifteen miRNAs were upregulated on GD13 and 5 miRNAs were downregulated on GD15 in 6-MP treatment rat placentas. Some miRNAs may have functions in apoptosis (miR-195, miR-21, miR-29c and miR-34a), inflammation (miR-146b), and ischemia (miR-144 and miR-451). In the maternal plasma, expression of miR-144 was significantly reduced by 6-MP treatment when examined by real-time RT-PCR. We determined toxicity-related gene expression in the rat placenta. Gene expression analysis was carried out by DNA oligo microarray using rat placenta total RNAs. Compared between predicted targets of miRNAs and microarray data in 6-MP-treated rat placenta, expressions of hormone receptor genes (estrogen receptor 1; Esr1 , progesterone receptor; Pgr , and prolactin receptor; Prlr ), xanthine oxidase ( Xdh ), Slc38a5 and Phlda2 genes were changed. The histopathologically found increase in trophoblastic giant cells and reduced placental growth by 6-MP treatment were well correlated to these gene expressions. These data suggest that some miRNAs may link to toxicological reactions in 6-MP-induced placental toxicity.
机译：microRNA（miRNA）是19-25个核苷酸的小单链RNA，在后颅面调节中是重要的。最近，据报道，MiRNA在毒性发病率中的作用是基因表达的关键止动符的调节因子，但MiRNA的详细机制尚未熟知。 6-巯基嘌呤（6-MP），抗白血病和免疫抑制药物，产生致畸性和妊娠损失。我们专注于胎盘来评估胚胎/胎儿发育的毒性，由6MP治疗产生。胎盘中的miRNA表达被MiRNA微阵列分析。将十五个miRNA在GD13上上调，在6MP处理大鼠胎盘中的GD15下调5名MIRNA。一些miRNA可以具有细胞凋亡（miR-195，miR-21，miR-29c和miR-34a）的功能，炎症（miR-146b）和缺血（miR-144和miR-451）。在母体等离子体中，当通过实时RT-PCR检查时，MiR-144的表达明显减少6-MP处理。我们确定大鼠胎盘中的毒性相关基因表达。使用大鼠胎盘总RNA通过DNA oligo微阵列进行基因表达分析。比较6-MP处理的大鼠胎盘中的miRNA和微阵列数据的预测靶，激素受体基因的表达（雌激素受体1; ESR1，孕酮受体; PGR和催乳素受体; PRLR），黄嘌呤氧化酶（XDH），SLC38A5和伯纳2基因发生了变化。通过6-MP处理的组织病理学发现的滋鸡巨细胞增加和降低胎盘生长的增加与这些基因表达良好。这些数据表明，一些miRNA可以在6mp诱导的胎盘毒性中链接到毒理学反应。

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