氧化应激状态下仔猪海马差异表达miRNAs与转录组的关联分析

Association Analysis of Differentially Expressed miRNAs and Transcriptomics in Piglet Hippocampus under Oxidative Stress

旨在解析仔猪脑海马背、腹侧区域参与氧化应激反应的小RNA(miRNA)靶基因及可能的调节机制。本研究基于前期投放到基因表达数据库(GEO)中的miRNAs和转录组数据包,采用生物信息学分析方法,对氧化应激荣昌仔猪脑海马背、腹侧区域差异表达的miRNA进行靶基因预测,并将预测的结果和转录组数据进行重叠筛选,将筛选得到的miRNA-mRNA构建互作网络图,并对靶基因进行GO分类和KEGG分析,以期探索仔猪脑海马背、腹侧区域中参与氧化应激调控的分子机制。结果表明,氧化应激分别引起了仔猪脑海马背侧309对和腹侧247对负向调控的miRNA-mRNA差异表达,其中,已知的差异表达miRNAs(DE miRNAs)负向调控差异表达mRNA(DE mRNAs)的互作网络背侧有67对(2对上调miRNA-下调mRNA,65对下调miRNA-上调mRNA),腹侧有41对(3对上调miRNA-下调mRNA,38对下调miRNA-上调mRNA)。GO分类和KEGG分析结果显示,miRNA靶向上调的基因主要调节氧化应激损伤和维持机体稳态;而靶向下调的基因,背侧主要调节细胞凋亡,腹侧主要调节细胞增殖、迁移等。并且部分DE miRNAs能够通过对基因的靶向调节协同或发散地参与对氧化应激相关神经系统疾病的调控。本研究首次描述了仔猪脑海马中与氧化应激相关的miRNA-mRNA的相互作用网络和信号通路,剖析了仔猪海马背、腹侧对氧化应激调节的差异性和一致性,为氧化应激介导的神经性疾病病理机制的研究奠定了基础。

This study aims to elucidate the target genes of microRNA(miRNA)involved in the oxidative stress reaction in the dorsal and ventral hippocampus of piglets and its possible regulatory mechanism.In the study,based on the data of miRNAs and transcriptome packets previously put into the gene expression database(GEO),the target genes of differentially expressed miRNAs in the dorsal and ventral regions of the hippocampus of Rongchang piglets under oxidative stress were predicted by bioinformatics analysis.The predicted results and transcriptome data were overlapped and screened to get the target pairs,which were used to construct a network map of miRNA-mRNA interaction.GO classification and KEGG analysis were performed to explore the molecular mechanisms involved in the regulation of oxidative stress in the dorsal and ventral regions of the hippocampus of piglets.The results showed that the oxidative stress-induced differential expression of 309 pairs of miRNAs-mRNAs in the dorsal hippocampus and 247 pairs in the ventral hippocampus of piglets.Among those,there were 67 pairs of negatively regulated miRNA-mRNAs in the dorsal hippocampus(2 pairs of up-regulated miRNA-down-regulated mRNAs,65 pairs of down-regulated miRNA-up-regulated mRNAs),and 41 pairs in the ventral hippocampus(3 pairs of up-regulated miRNA-down-regulated mRNAs,38 pairs of down-regulated miRNA-up-regulated mRNAs).GO classification and KEGG analysis results displayed that targeted up-regulated genes played a major role in regulating oxidative stress damage and maintaining body homeostasis,while targeted down-regulated genes in the dorsal hippocampus mainly regulated cell apoptosis and those in the ventral hippocampus mainly regulated cell proliferation and migration.And some differentially expressed miRNAs participated in the regulation of oxidative stress-related neurological diseases in a coordinated or divergent manner through targeting regulating genes.In conclusion,the study firstly described the interaction network and signaling pathway of oxidative stress-related miRNA-mRNAs in the hippocampus of piglets,and analyzed the differences and consistency in the regulation of oxidative stress in the dorsal and ventral hippocampus,which laid a foundation for the study of the pathological mechanism of oxidative stress-mediated neurological diseases.