【摘要】：目的重注釋甲基化數(shù)據(jù)并構(gòu)建microRNA(miRNA)基因甲基化譜,探究差異甲基化miRNA在顳葉癲癇(TLE)發(fā)生發(fā)展及耐藥機(jī)制中的作用。方法收集TLE患者以及健康對(duì)照外周血,提取DNA進(jìn)行全基因組DNA甲基化檢測(cè)。將甲基化數(shù)據(jù)重注釋至miRNA基因,統(tǒng)計(jì)分析篩選病例組與對(duì)照組以及臨床亞組之間的差異甲基化miRNA,運(yùn)用生物信息學(xué)方法對(duì)差異甲基化miRNA功能分析。結(jié)果 TLE和對(duì)照組間有82個(gè)miRNA基因甲基化存在差異(FDR5%),其中甲基化升高的70個(gè)。臨床亞組間也存在差異甲基化miRNA基因(P0.01)。差異甲基化miRNA基因參與MAPK信號(hào)通路、神經(jīng)營(yíng)養(yǎng)信號(hào)通路等多條生物學(xué)通路。結(jié)論 TLE患者外周血miRNA基因組甲基化存在異常,以甲基化程度升高為主。差異甲基化miRNA基因參與多條生物學(xué)通路,可能在TLE發(fā)病及耐藥機(jī)制中起到重要作用。
[Abstract]:Objective to reinterpret the methylation data and construct the methylation spectrum of microRNA (miRNA) gene to explore the role of differential methylation miRNA in the pathogenesis and drug resistance of (TLE) in temporal lobe epilepsy. Methods Peripheral blood samples from patients with TLE and healthy controls were collected and DNA was extracted for genomic DNA methylation detection. The methylation data were reannotated to miRNA gene, and the differential methylation miRNA, was selected between the case group, control group and clinical subgroup. The function of differential methylation miRNA was analyzed by bioinformatics. Results there were 82 miRNA gene methylation differences (FDR5%) between TLE and control group, 70 of them had higher methylation. There were also differences between clinical subgroups in methylation of miRNA gene (P0.01). Differentially methylated miRNA gene is involved in many biological pathways, such as MAPK signaling pathway and neurotrophic signaling pathway. Conclusion miRNA genomic methylation in peripheral blood of patients with TLE is abnormal and the degree of methylation is increased. Differential methylation of miRNA gene may play an important role in the pathogenesis and drug resistance of TLE.
【作者單位】： 中南大學(xué)湘雅醫(yī)院神經(jīng)內(nèi)科;
【基金】：國(guó)家自然科學(xué)基金項(xiàng)目(81371435;81671299;81401078) 國(guó)家科技部重大研究專項(xiàng)《基于組學(xué)特征譜的癲癇分子分型研究》(2016YFC0904400)
【分類號(hào)】：R742.1

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