Abstract：
Atrazine (ATR) is a widely applied herbicide in Asia and South America with slow natural degradation and documented deleterious effects on human and animal health, including hippocampal toxicity. However, relatively little is known about the molecular mechanisms responsible for ATR-induced hippocampal damage. Screening for differentially expressed mRNAs and microRNAs (miRNAs), and construction of potential miRNA-mRNA regulatory networks can reveal such mechanisms, so we analyzed the mRNA and miRNA expression profiles of rat hippocampus-derived H19-7 cells in response to ATR (500 μM) and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment (KEGG) analyses. Integration of miRNA sequencing (miRNA-seq) and mRNA sequencing (mRNA-seq) results identified 114 differentially expressed miRNAs (DEMIs, 40 upregulated and 74 downregulated), and 510 differentially expressed mRNAs (DEMs, 177 upregulated and 333 downregulated) targeted by these DEMIs. The top 10 hub mRNAs (Fos, Prkcb, Ncf1, Vcam1, Atf3, Pak3, Pak1, Cacna1s, Junb, and Ccl2) and 19 related miRNAs (rno-miR-194-5p, rno-miR-24-3p, rno-miR-3074, rno-miR-1949, rno-miR-218a-1-3p, rno-miR-1843a-5p, rno-miR-1843b-5p, rno-miR-296-3p, rno-miR-320-3p, rno-miR-219a-1-3p, rno-miR-122-5p, rno-miR-1839-5p, rno-miR-1843a-3p, rno-miR-215, rno-miR-3583-3p, rno-miR-194-3p, rno-miR-128-1-5p, rno-miR-1956-5p, and rno-miR-466b-2-3p) were validated by quantitative real-time PCR. GO analysis indicated that these DEMs were enriched in genes associated with synaptic plasticity and antioxidant capacity, while KEGG analysis suggested that enriched DEMs were involved in calcium signaling, axon guidance, MAPK signaling, and glial carcinogenesis. The miRNA-mRNA regulatory network identified here may provide potential biomarkers and novel strategies for the treatment of hippocampal neurotoxicity induced by ATR.
摘要：
阿特拉津（ATR）是在亚洲和南美洲广泛使用的除草剂，具有缓慢的自然降解和对人类和动物健康的有害影响。包括海马毒性.然而,对ATR诱导的海马损伤的分子机制知之甚少.筛选差异表达的mRNA和微小RNA（miRNA），潜在的miRNA-mRNA调控网络的构建可以揭示这些机制，因此，我们分析了大鼠海马来源的H19-7细胞响应ATR（500μM）的mRNA和miRNA表达谱，并进行了基因本体论（GO）和京都基因和基因组富集百科全书（KEGG）分析。miRNA测序（miRNA-seq）和mRNA测序（mRNA-seq）的整合结果鉴定出114个差异表达的miRNA（DEMIs，40上调和74下调)，和510种差异表达的mRNA(DEM，177个上调和333个下调)由这些DEMIs靶向。前10名枢纽mRNA(Fos，Prkcb,Ncf1,Vcam1,Atf3,Pak3,Pak1,Cacna1s,Junb,和Ccl2）和19个相关的miRNA（rno-miR-194-5p，rno-miR-24-3p,rno-miR-3074,rno-miR-1949,rno-miR-218a-1-3p,rno-miR-1843a-5p,rno-miR-1843b-5p,rno-miR-296-3p,rno-miR-320-3p,rno-miR-219a-1-3p,rno-miR-122-5p,rno-miR-1839-5p,rno-miR-1843a-3p,rno-miR-215,rno-miR-3583-3p,rno-miR-194-3p,rno-miR-128-1-5p,rno-miR-1956-5p,和rno-miR-466b-2-3p）通过定量实时PCR进行验证。GO分析表明，这些DEM富含与突触可塑性和抗氧化能力相关的基因，虽然KEGG分析表明，富集的DEM参与钙信号传导，轴突引导,MAPK信号，和胶质细胞癌变。本文鉴定的miRNA-mRNA调控网络可能为ATR诱导的海马神经毒性的治疗提供潜在的生物标志物和新策略。
