摘要目的 探索miRNA-155对急性髓系白血病患者预后影响及可能分子机制。方法 下载TCGA数据库中急性髓系白血病患者的miRNA和RNA表达谱及临床数据,按照miRNA-155表达水平高低排序,将前50%分为高表达组(n=81),剩余为低表达组(n=81),比较两组患者生存时间,将患者各RNA表达水平逐一与miRNA-155表达水平进行Pearson相关性检测,根据相关系数分别选取与miRNA-155正相关和负相关的前50个基因,使用STRING工具完成KEGG通路和GO富集分析,并构建蛋白相互作用网络。结果 miRNA-155低表达组中位生存时间高于miRNA-155高表达组,差异有统计学意义(609 d vs 485 d,P<0.05)。在检测的19448个基因中,21号染色体开放阅读框71(C21orf71)与miRNA-155正相关系数最高(r=0.634,P<0.05);溶质载体家族13成员5(SLC13A5)与miRNA-155负相关系数最高(r=-0.50,P<0.05)。GO富集分析和KEGG通路富集分析可见,相关基因主要涉及的生物学过程包括DNA复制启动与DNA链延伸;主要涉及的分子功能为解旋酶活性和作用于DNA的催化活性;主要涉及的细胞组分为微染色体维持复合体和三级颗粒;主要涉及的信号通路为DNA复制和细胞周期调控。微小染色体维持蛋白(MCM)基因家族是处于蛋白相互作用网络的核心。结论 miRNA-155过表达与远期生存率降低有关,这可能与其调控细胞DNA复制有关。
Abstract：Objective To investigate the effect of miRNA-155 on prognosis of acute myeloid leukemia (AML) patients and its possible mechanism.Methods The miRNA and RNA expression profiles and clinical data of patients with AML in the TCGA database were downloaded. According to the expression level of miRNA-155, the first 50% were assigned to the high expression group (n=81), while the rest were assigned to the low expression group (n=81). The survival time of the two groups was compared. Pearson correlation analysis was used to detect the expression level of each RNA and miRNA-155, and the top 50 genes either positively or negatively correlated with miRNA-155 were selected according to the correlation coefficients. Analysis of the KEGG pathway and GO enrichment, as well as the protein interaction networks, were completed by the STRING tool.Results The median survival time in the low expression group was longer than that of the high expression group (609 d vs 485 d,P<0.05). Among the 19448 genes detected, the positive correlation coefficient of chromosome 21 open reading frame 71(C21orf71) was the highest(r=0.634,P<0.05), so was the negative correlation coefficient of solute carrier family 13 member 5 (SLC13A5) (r=-0.50,P<0.05).The GO enrichment analysis and the KEGG pathway enrichment analysis showed that the main biological processes involved were DNA replication initiation and DNA strand extension, the main molecular functions involved were the activity of helicase and the catalytic activity of DNA, the main cell components involved were microchromosome maintenance complex and tertiary granules, and the main signaling pathways involved were DNA replication and cell cycle regulation.The microchromosome maintenance protein(MCM) gene family was at the core of the protein interaction network.Conclusions Overexpression of miRNA-155 is associated with decreased long-term survival, which may be related to its regulation of cellular DNA replication.
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