宋杨, 于明. miR-182-5p在阿尔兹海默病的表达及生物信息学分析[J]. 蚌埠医科大学学报, 2022, 47(12): 1628-1632. DOI: 10.13898/j.cnki.issn.1000-2200.2022.12.003
    引用本文: 宋杨, 于明. miR-182-5p在阿尔兹海默病的表达及生物信息学分析[J]. 蚌埠医科大学学报, 2022, 47(12): 1628-1632. DOI: 10.13898/j.cnki.issn.1000-2200.2022.12.003
    SONG Yang, YU Ming. Expression and bioinformatics analysis of miR-182-5p in Alzheimer's disease[J]. Journal of Bengbu Medical University, 2022, 47(12): 1628-1632. DOI: 10.13898/j.cnki.issn.1000-2200.2022.12.003
    Citation: SONG Yang, YU Ming. Expression and bioinformatics analysis of miR-182-5p in Alzheimer's disease[J]. Journal of Bengbu Medical University, 2022, 47(12): 1628-1632. DOI: 10.13898/j.cnki.issn.1000-2200.2022.12.003

    miR-182-5p在阿尔兹海默病的表达及生物信息学分析

    Expression and bioinformatics analysis of miR-182-5p in Alzheimer's disease

    • 摘要:
      目的探究miR-182-5p在阿尔兹海默病(AD)病人血清中的表达水平,并采用生物信息学方法对其进行靶基因预测及功能分析。
      方法从GEO数据库获取AD相关miRNAs芯片数据集GSE104514,利用GEO2R在线工具分析差异表达的miRNAs,选择差异最大的miR-182-5p进行深入研究。收集AD病人28例(AD组)及健康者15名(对照组),应用实时荧光定量聚合酶链反应法检测血清中miR-182-5p的表达水平。通过miRBase数据库分析miR-182-5p在不同物种间的保守性;运用miRcode、miRDB、miRWalk和Target Scan数据库预测miR-182-5p靶基因,并取交集靶基因;应用DAVID和KOBAS数据库对miR-182-5p靶基因进行GO功能及KEGG信号通路富集分析。
      结果AD小鼠脑组织的miR-182-5p表达明显高于野生型小鼠(P < 0.05),AD病人血清中的miR-182-5p表达量(2.022±1.225)明显高于对照组(0.486±0.442)(P < 0.01);保守性分析显示miR-182-5p成熟体序列在不同物种间高度保守;在线数据库预测获得miR-182-5p潜在的交集靶基因共23个。GO富集结果显示,miR-182-5p靶基因主要参与于锌离子的结合、生物过程的负调控、杂环类化合物的结合、主要代谢过程的调节、GTPase的活性、膜的内在成分的组成、大脑的发育、部分细胞形态的发生、转移酶的活性、信号的调节、泛素结合酶的结合、耳蜗的发育、组蛋白H4-K16的乙酰化作用、咽系统的发育、神经元演化方向的规范、大脑皮层细胞的迁移、大脑皮层细胞的放射状定向迁移等多个生物学过程。KEGG分析结果显示,miR-182-5p靶基因主要参与肾集合管的酸分泌、醚脂类代谢、志贺菌病、细胞的黏附、细菌侵袭上皮细胞等5条信号通路。
      结论miR-182-5p在AD病人血清中高表达,其可能通过多条信号通路参与AD的发展过程。

       

      Abstract:
      ObjectiveTo investigate the expression level of miR-182-5p in the peripheral blood serum of patients with Alzheimer's disease(AD), predict its target genes and conduct functional analysis by bioinformatics methods.
      MethodsThe dataset of GSE104514 was searched and downloaded from the GEO database. The differentially expressed miRNAs of the dataset were analyzed by GEO2R tool. Among which, miR-182-5p was the most differentially expressed miRNA and was selected for in-depth analysis. Fifteen normal controls(NC) and twenty-eight patients with AD were enrolled in this study. The expression levels of miR-182-5p in peripheral blood serum were determined by real-time fluorescent quantitative PCR. MiRBase database was used to analyze the conservativeness of miR-182-5p among different species. miRcode, miRDB, miRWalk and Target Scan databases were performed to predict the target genes of miR-182-5p, and the common target genes of these databases were screened out. GO and KEGG functional enrichment analysis of miR-182-5p target genes were conducted by DAVID and KOBAS databases.
      ResultsThe expression of miR-182-5p in brain tissue of AD mice was higher than that in wild mice(P < 0.05). The expression level of miR-182-5p in the peripheral blood serum of AD patients(2.022±1.225) was significantly higher than that of the control group(0.486±0.442)(P < 0.01). Conservative analysis showed that the mature sequence of miR-182-5p was highly conserved in different species. A total of 23 potential intersection target genes of miR-182-5p were predicted by the online databases. The results of GO enrichment analysis suggested that the target genes of miR-182-5p were mainly enriched in zinc ion binding, negative regulation of biological process, heterocyclic compound binding, regulation of primary metabolic process, GTPase activity, intrinsic component of membrane, brain development, cell part morphogenesis, transferase activity, regulation of signaling, ubiquitin conjugating enzyme binding, cochlea development, histone H4-K16 acetylation, pharyngeal system development, neuron fate specification, cerebral cortex cell migration, and cerebral cortex radially oriented cell migration, etc. The results of KEGG signal pathway showed that target genes were mainly enriched in 5 signal pathways, including acid secretion of renal collecting tube, ether lipid metabolism, Shigellosis, adhesion of cell mucosa, and bacterial invasion of epithelial cells.
      ConclusionsMiR-182-5p is highly expressed in the peripheral blood serum of AD patients and may participate in the development of AD through multiple signaling pathways.

       

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