基于生物信息学数据库的结肠癌SDC4基因表达调控机制及作用研究

The Study on the Expression Regulation Mechanism and the Role of SDC4 Gene in Colon Cancer Based on Bioinformatics Databases

为了揭示SDC4基因在结肠癌中的功能及其表达调控机制.通过GEPIA2、Ualcan与Oncolnc等数据库研究分析SDC4基因在结肠癌的表达及其对患者总生存期的影响.通过Wanderer、UCSC、Cistrome DB、miRcode和miRDB等数据库研究分析结肠癌SDC4基因启动子区的甲基化、组蛋白修饰,调控其表达的转录因子和miRNAs.通过GEPIA2、Ualcan、HCMdb与DAVID等数据库研究分析在结肠癌中与SDC4基因共表达的基因及其生物学作用.基于以上生物信息学数据库,研究发现,在结肠癌中:SDC4基因的表达水平显著增高,并与肿瘤组织分期、淋巴结转移正相关,与患者预后负相关.SDC4基因启动子区的甲基化水平显著升高,转录激活性组蛋白修饰H3K4Me1与H3K27Ac显著富集.SP1、TEAD4、JUND、FOSL1、NR1H3、PPARG、SRF、TFAP4共8个转录因子可能调控SDC4基因的转录表达.与此同时hsa-miR-194和hsa-miR-124也可能调控SDC4基因表达.hsa-miR-194和hsa-miR-124的表达下调.SERINC3、DNTTIP1、ATP9A、CHMP4B、BCL2L1、STAU1、SYS1、YWHAB、OSBPL2、SLC35C2、TM9SF4与SDC4基因共表达.SDC4基因可能参与调控结肠癌细胞凋亡、细胞通讯、物质运输与定位等生物学过程.基于生物信息学数据库研究发现的结果,为进一步阐明SDC4基因在结肠癌中的功能及其表达调控机制提供重要的线索.

To investigate the expression regulation mechanism and the role of SDC4 gene in colon cancer,GEPIA2 database,Ualcan database and Oncolnc database were used to study the expression of SDC4 gene in colon cancer and its effect on overall survival of the patients.Wanderer database,UCSC database,Cistrome DB database,miRcode database and miRDB database were used to study methylation and histone modification of the promoter region of SDC4 gene,and transcription factors and miRNAs for regulating the gene expression.GEPIA2 database,Ualcan database,HCMdb database and DAVID database were used to analyze genes co-expressed with SDC4 gene and the biological processes where these gene were involved in the colon cancer.The following results were found in colon cancer through the usage of the above bioinformatics database:The expression of SDC4 gene was significantly higher than that in adjacent normal tissues,and was positively correlated with tissue stage and lymph node metastasis,and negatively correlated with prognosis of patients in colon cancer.The methylation level of SDC4 gene promoter region was elevated in colon cancer.Histone modifications in transcriptional activation of H3K4Me1 and H3K27Ac were significantly enriched in the promoter of the SDC4 gene.A total of 8 transcription factors including SP1,TEAD4,JUND,FOSL1,NR1H3,PPARG,SRF,and TFAP4 might transcriptionally regulate the expression of SDC4 gene in colon cancer.Meanwhile,hsa-miR-194 and hsa-miR-124 might also regulate SDC4 gene expression.The expression of hsa-miR-194 and the expression of hsa-miR-124 were down-regulated in colon cancer.A total of 11 genes,namely SERINC3,DNTTIP1,ATP9A,CHMP4B,BCL2L1,STAU1,SYS1,YWHAB,OSBPL2,SLC35C2,and TM9SF4 were co-expressed with SDC4 gene in colon cancer.SDC4 gene was possibly involved in the regulation of biological processes such as apoptosis,cell communication,material transport and localization in colon cancer cells.The findings based on the bioinformatics database can provide important clues for further elucidating the regulatory mechanism and role of SDC4 gene expression in colon cancer.