噪声性听力损失大鼠耳蜗miRNA调控网络分析

发布时间：2018-04-01 17:19

本文选题：噪声性听力损失　切入点：下一代sRNA测序　出处：《现代预防医学》2016年01期

【摘要】：目的通过噪声性听力损失(NIHL)耳蜗差异性mi RNA构建的基因调控网络,分析NIHL耳蜗的重要基因及功能,探讨NIHL的损伤机制。方法 6只SPF及SD大鼠通过110 d B SPL(6 h/d、24 d)的高斯白噪声暴露建立NIHL模型,6只SPF及SD大鼠非噪声暴露作对照,噪声暴露后7 d取实验大鼠耳蜗组织进行s RNA深度测序,分析差异性表达的mi RNA,以差异最显著的8个mi RNA依据靶基因数据库Target Scan、mi Randa和mi RDB共同预测的靶基因建立差异性表达mi RNA的靶基因集,结合蛋白互作数据库构建mi RNA调控网络,统计网络中每个基因相连基因的个数,确定相连基因个数大于30的基因作为NIHL大鼠耳蜗的重要基因,通过Gene Cards数据库对重要基因进行功能注释。结果 (1)噪声暴露组大鼠永久性听阈位移水平(PTS)明显高于对照组(秩和检验:Z值-2097,P0.01);(2)s RNA测序结果显示2组耳蜗差异性mi RNA有148个[|log2(Fold Change)|1],差异性最显著的8个mi RNA为:rno-mi R-378b、rno-mi R-211-5p、rno-mi R-133b-3p、rno-mi R-29c-3p、rno-let-7c-2-3p、rno-mi R-674-5p、rno-mi R-495、rno-mi R-3068-3p;(3)mi RNA调控网络中的重要基因有11个:VEGFA、TNF、EGFR、FOS、NR3C1、AGT、CREBBP、PTK2、CD44、STAT3、IGF1。结论 NIHL大鼠耳蜗的11个重要基因通过调控细胞增殖与分化、控制细胞凋亡、改善组织细胞营养代谢、介导组织炎性反应以改善和修复耳蜗组织细胞。
[Abstract]:Objective to analyze the important genes and functions of NIHL cochlea and explore the mechanism of NIHL damage by using the gene regulatory network constructed by the difference mi RNA of noise-induced hearing loss (NHL) cochlea.Methods six SPF and SD rats were exposed to white noise at 110d B SPL(6 / dago for 24 days to establish NIHL model. Six SPF and SD rats were exposed to non-noise as control. Cochlear tissues of experimental rats were taken 7 days after noise exposure for deep sequencing of s RNA.Based on the target genes predicted by Target Scanmi Randa and mi RDB, the target gene sets of differentially expressed mi RNA were established by using the 8 miRNAs with the most significant difference. The regulatory network of mi RNA was constructed by combining the protein interaction database with the target genes predicted by Target Scanmi Randa and mi RDB.The number of genes connected to each gene in the network was counted, and the genes with more than 30 connected genes were identified as important genes in cochlea of NIHL rats. The important genes were annotated by Gene Cards database.Results (1) the permanent threshold displacement level of noise exposure group was significantly higher than that of the control group (rank sum test: Z value -2097 P0.01P0.01P0.01) RNA sequencing results showed that the cochlear difference mi RNA of the two groups was 148 [log2(Fold change] 1. The most significant difference of 8 mi RNA was: 1: rno-mi.Conclusion 11 important genes of NIHL rat cochlea can regulate cell proliferation and differentiation, control cell apoptosis, improve nutrient metabolism of tissue cells, and mediate inflammatory response in order to improve and repair cochlear histocytes.
【作者单位】：深圳龙岗区疾病控制中心;广东药学院公共卫生学院;广州市职业病防治院;
【基金】：国家自然科学基金(81202179) 广东省自然科学基金(S2012040006490) 广东药学院科技处-附属第一医院联合自然科学培育基金(GYFYLH201326)
【分类号】：R764

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