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目的重注释甲基化数据并构建microRNA(miRNA)基因甲基化谱,探究差异甲基化miRNA在颞叶癫痫(TLE)发生发展及耐药机制中的作用。方法收集TLE患者以及健康对照外周血,提取DNA进行全基因组DNA甲基化检测。将甲基化数据重注释至miRNA基因,统计分析筛选病例组与对照组以及临床亚组之间的差异甲基化miRNA,运用生物信息学方法对差异甲基化miRNA功能分析。结果 TLE和对照组间有82个miRNA基因甲基化存在差异(FDR<5%),其中甲基化升高的70个。临床亚组间也存在差异甲基化miRNA基因(P<0.01)。差异甲基化miRNA基因参与MAPK信号通路、神经营养信号通路等多条生物学通路。结论 TLE患者外周血miRNA基因组甲基化存在异常,以甲基化程度升高为主。差异甲基化miRNA基因参与多条生物学通路,可能在TLE发病及耐药机制中起到重要作用。
Objective To re-annotate methylation data and construct the microRNA (miRNA) gene methylation profile to explore the role of differentially methylated miRNAs in the development of the temporal lobe epilepsy (TLE) and drug resistance mechanisms. Methods TLE patients and healthy control peripheral blood were collected and DNA was extracted for genome-wide DNA methylation detection. The methylation data were re-annotated to miRNA genes, and the differential methylation miRNAs were screened by statistical analysis between the case group and the control group and the clinical subgroups. The differential methylation miRNA function analysis was performed by bioinformatics methods. Results There were 82 miRNA gene methylation differences (FDR <5%) between TLE and control group, of which 70 were methylated. There was also a difference in methylated miRNA genes between clinical subgroups (P <0.01). Differentially methylated miRNA genes are involved in multiple biological pathways such as MAPK signaling and neurotrophic signaling. Conclusion There is abnormal methylation of miRNA in peripheral blood of patients with TLE, with the increase of methylation. Differential methylation of miRNA genes involved in multiple biological pathways, may play an important role in the pathogenesis of TLE and drug resistance mechanisms.