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作 者:曹辉[1] 许钟[2] 陈燕平[1] 张玲玲[2] 鲁亮[1] Cao Hui;Xu Zhong;Chen Yanping(Dept of Oncology,Guizhou Provincial People's Hospital,Guiyang 550002;Dept of Gastroenterology,Guizhou Provincial People's Hospital,Guiyang 550002)
机构地区:[1]贵州省人民医院肿瘤科,贵阳550002 [2]贵州省人民医院消化内科,贵阳550002
出 处:《安徽医科大学学报》2020年第1期80-83,共4页Acta Universitatis Medicinalis Anhui
基 金:国家自然科学基金(编号:81860439);贵州省科学技术基金(编号:黔科合J字[2012]2241号)
摘 要:目的应用生物信息学数据库挖掘数据,预测分析肝细胞癌发生发展过程中抑癌基因肝核转录因子4α(HNF4α)表达下调的转录调控机制。方法从美国国家生物技术信息中心在线核苷酸数据库获得HNF4α基因的启动子序列;应用Promotor Scan、Patch、P-Match、Ali Baba2等在线转录因子预测软件分析HNF4α转录因子结合位点;应用在线肝脏基因数据库liveratlas筛查肝癌组织中表达下调的基因,与预测的转录因子进行对比。通过TCGA数据库提取相关转录因子与HNF4α的肝癌组织芯片表达结果,进行相关性分析。结果人HNF4α基因在肝癌中对应转录本的启动子约1471 bp。应用Promotor Scan、Patch、P-Match和Ali Baba2等在线软件分析,预测转录因子结合位点结果汇总后去除重复,共涵盖225个转录因子。应用在线基因数据库liveratlas检索,提取肝细胞癌中表达下调的基因共2 538个,与上述预测的225个转录因子进行对比,取交集获得目标转录因子共17个。相关性分析提示HLF (r=0. 553 4)、RREB1 (r=0. 407 9)、RXRA(r=0. 424 7)等转录因子与HNF4α的表达成正相关。结论生物信息学分析提示HLF、RREB1、RXRA等转录因子参与HNF4α在肝脏中表达的转录调控,其中一个或多个蛋白的低表达与肝细胞癌发生发展中抑癌基因HNF4α的表达下调有关。Objective To predict and analyze the mechanism of downregulation of HNF4α expression in hepatocellular carcinoma(HCC) by bioinformatics analysis. Methods The promoter sequence of HNF4α gene obtained from NCBI GenBank was analyzed by transcription factor prediction software, including PromotorScan, Patch, P-Match and AliBaba2. Meanwhile, the down-regulated genes in human HCC were screened by Liveratlas. Then the intersected genes were analyzed based on the data extracted from TCGA database. Results The promoter of the corresponding transcript of human HNF4α gene in HCC is about 1 471 bp. After removing duplication, the pool of predicting transcription factor binding sites covers 225 transcription factors by using online software. A total of 2 538 down-regulated genes in HCC were extracted from liveratlas online gene database, and 17 transcription factors were obtained by compared with the transcription factor pool predicted above. The correlation analysis indicated that HLF(r=0.553 4), RREB1(r=0.407 9) and RXRA(r=0.424 7) were positively correlated with the expression of HNF4α. Conclusion Bioinformatics analysis indicates that HLF, RREB1 and RXRA may be involved in the transcriptional regulation of HNF4α expression in liver. The faint expression of one or more of them may be related to the down-regulation of HNF4α expression in the development of HCC.
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