人丝裂原活化蛋白激酶相关蛋白1在肝细胞癌中转录调控的生物信息学分析

Bioinformatics analysis of transcriptional regulation of mitogen-activated protein kinase-associated protein 1 in human hepatocellular carcinoma

目的利用生物信息学技术分析及预测人丝裂原活化蛋白激酶相关蛋白1(MAPKAP1)基因表达有关的转录调控机制,为深入研究人MAPKAP1基因与肝癌的关系提供基础。方法从美国国家生物技术信息中心在线核苷酸数据库(Gene Bank)检索人MAPKAP1基因,获得其基因启动子区序列;通过在线软件预测分析启动子区转录因子结合位点,应用在线基因数据库Liveratlas提取肝癌组织中表达上调的基因,取交集获得目标转录因子。通过TCGA数据库提取筛选出的转录因子与MAPKAP1的肝癌基因芯片表达结果,采用GraphPad Prism 5统计软件行相关性分析。结果人MAPKAP1基因在肝脏及肝癌中转录本全长1689 bp,位于转录起始位点-1470 bp至+218 bp。取交集获得目标转录因子共有13个,即C/EBP、CNBP、CTCF、DBP、IRF2、LEF1、NF1、NFKB1、PAX8、SMAD4、Sp3、SRF、YY1。相关性分析显示,转录因子C/EBP、DBP、LEF1与MAPKAP1表达呈正相关(r分别为0.1513、0.2356、0.1553,P均﹤0.01),CNBP、CTCF、IRF2、NF1、NFKB1、PAX8、SMAD4、Sp3、SRF、YY1与MAPKAP1表达无明显相关(P均﹥0.05)。结论通过生物信息学技术分析及预测,在人肝癌中C/EBP、DBP、LEF1与MAPKAP1表达呈正相关,这些转录因子可能参与MAPKAP1基因表达的转录调控。

Objective To predict and analyze the mechanism of transcriptional regulation of the mitogen-activated protein kinase-associated protein 1(MAPKAP1)in the human hepatocellular carcinoma(HCC)cells by bioinformatics analysis.Methods The promoter sequence of MAPKAP1 gene obtained from NCBI GenBank was analyzed by transcription factor prediction software,including PromotorScan,Patch,and P-Match.Meanwhile,the up-regulated genes in human HCC were screened by Liveratlas.Then the intersected genes based on the data extracted from TCGA database were analyzed by GraphPad Prism 5 statistical software.Results The promoter of the corresponding transcript of human MAPKAP1 gene in HCC was about 1689 bp.Thirteen target transcription factors,including C/EBP,CNBP,CTCF,DBP,IRF2,LEF1,NF1,NFKB1,PAX8,SMAD4,Sp3,SRF,and YY1,were obtained.The correlation analysis indicated that C/EBP(r=0.1513),DBP(r=0.2356),and LEF1(r=0.1553)were positively correlated with the expression of MAPKAP1(all P<0.01);CNBP,CTCF,IRF2,NF1,NFKB1,PAX8,SMAD4,Sp3,SRF,and YY1 were not related to MAPKAP1expression(all P>0.05).Conclusion Bioinformatics analysis indicates that C/EBP,DBP,and LEF1 are positively correlated with MAPKAP1 expression,which may participate in the transcriptional regulation of MAPKAP1 in HCC.