Molecular mechanism in the pathogenesis of mild chronic hepatitis B based on microRNA regulation
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摘要: 目的从microRNA(miRNA)调控角度揭示轻度慢性乙型肝炎发病的分子机制。方法收集2013年7月-2014年2月成都市传染病医院门诊就诊的患者共16例,分为轻度慢性乙型肝炎组与正常组,借助Agilent Human miRNA 8×60 k微阵列芯片检测血浆中miRNA表达谱,求得两组间差异表达的miRNA谱,借助miRNA生物信息学分析软件预测其靶基因并对靶基因进行GO功能富集分析和pathway分析。两组间比较采用t检验,多组间比较采用方差分析。结果两组间的差异表达miRNAs共54条(P值均<0.05),30条上调,24条下调;其功能主要涉及细胞增殖、转录正/负调控、生物合成过程的正/负调控、蛋白质定位、Wnt受体信号通路、转录正/负调控、基因表达的正/负调控、酶联受体蛋白信号通路、蛋白氨基酸的磷酸化等生命过程。Pathway分析得到其主要涉及Wnt信号通路、Notch信号传导途径、Hedgehog信号通路、p53信号通路、B淋巴细胞受体信号通路等。结论轻度慢性乙型肝炎发生受到特异性miRNA调控,涉及多个生命过程及通路。Abstract: Objective To investigate the molecular mechanism in the pathogenesis of mild chronic hepatitis B from the perspective of microRNA(miRNA) regulation.Methods A total of 16 patients who visited the outpatient service of Chengdu Hospital of Infectious Diseases from July 2013 to February 2014 were enrolled and divided into mild chronic hepatitis B group and normal group.The Agilent Human miRNA 8 × 60 k microarray chips were used to detect the expression profile of miRNA in plasma and obtain the profile of miRNAs expressed differentially between the two groups.The miRNA bioinformatics analysis software was used to predict target genes,and GO functional enrichment analysis and pathway analysis were performed for these target genes.An analysis of variance was used for comparison between multiple groups,and the t-test was used for comparison between two groups.Results A total of 54 miRNAs were differentially expressed between the two groups(all P < 0.05),and among them,30 were upregulated,and 24 were downregulated.The functions of these miRNAs included cell proliferation,positive / negative transcription regulation,positive / negative regulation of biosynthesis,protein localization,the Wnt receptor signaling pathway,positive / negative regulation of gene expression,the enzyme- linked receptor protein signaling pathway,and phosphorylation of protein amino acids.Pathway analysis revealed that miRNAs were mainly involved in the Wnt signaling pathway,Notch signal transduction pathway,Hedgehog signaling pathway,p53 signaling pathway,and B cell receptor signaling pathways,etc.Conclusion The pathogenesis of mild chronic hepatitis B is regulated by specific miRNAs and involves various life processes and pathways.
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Key words:
- hepatitis B /
- chronic /
- microRNAs
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