Key Laboratory of Green Pesticide and Agriculture Bioengineering, Ministry of Education, Guizhou University, Guiyang, China.
DNA Cell Biol. 2011 Dec;30(12):1073-83. doi: 10.1089/dna.2011.1267. Epub 2011 Jun 24.
Dichlorvos (DIC) is an organophosphate compound with cholinergic and noncholinergic neurotoxicity as well as non-neuronal cytotoxicity. Little is known about the mechanisms of DIC cytotoxicity in non-neuronal cells. In this study, we established a porcine kidney epithelial cell line (PK15) as a model to explore the mechanisms underlying DIC cytotoxicity based on miRNA and mRNA expression profiling analysis. We found that DIC inhibited the proliferation of PK15 cells in a dose- and time-dependent manner, which may result from apoptosis induced by DIC. Microarray analyses revealed that 16 and 14 miRNAs were significantly upregulated and downregulated in PK15 cells treated by 0.875 mM DIC for 8 h. Among the 30 differentially expressed miRNAs, 7 new miRNAs in pigs were predicted by homology-based searches. In addition, DIC upregulated 339 and downregulated 282 mRNA transcripts. A target prediction algorithm was used to analyze the pattern of differentially expressed miRNAs and mRNAs. Functional analysis indicated that these mRNAs belonged to different functional categories, forming a network participating in the DIC-induced apoptosis in PK15 cells. Therefore, our findings provide new insights into the role of miRNAs in the gene expression and function in DIC-related noncholinergic cytotoxicity.
敌敌畏(DIC)是一种有机磷化合物,具有胆碱能和非胆碱能神经毒性以及非神经元细胞毒性。目前对于 DIC 在非神经元细胞中的细胞毒性机制知之甚少。在这项研究中,我们建立了一个猪肾上皮细胞系(PK15)作为模型,通过 miRNA 和 mRNA 表达谱分析来探索 DIC 细胞毒性的机制。我们发现 DIC 以剂量和时间依赖的方式抑制 PK15 细胞的增殖,这可能是由 DIC 诱导的细胞凋亡引起的。微阵列分析显示,在 0.875 mM DIC 处理 8 小时的 PK15 细胞中,有 16 个和 14 个 miRNA 分别显著上调和下调。在 30 个差异表达的 miRNA 中,通过同源性搜索预测了 7 个猪的新 miRNA。此外,DIC 上调了 339 个和下调了 282 个 mRNA 转录本。使用靶标预测算法分析差异表达的 miRNA 和 mRNAs 的模式。功能分析表明,这些 mRNAs 属于不同的功能类别,形成一个参与 PK15 细胞中 DIC 诱导的细胞凋亡的网络。因此,我们的研究结果为 miRNA 在 DIC 相关非胆碱能细胞毒性中的基因表达和功能中的作用提供了新的见解。