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目的探讨MTA1对食管癌转移相关基因的影响。方法用RNA干扰的方法在食管癌细胞系KYSE150中沉默MTA1基因的表达,随后进行转移相关基因芯片分析。以两次芯片分析中均上调2倍以上(或下调1/2)为差异显著基因。通过DIVID生物信息学数据库进行gene ontology的通路分析。结果在两次基因芯片分析中均有意义上调的基因共有7个,分别是LAMC1、MMP14、MMP15、MDM2、API5、ODC1、PTGS2;而两次均显著下调的基因共有14个,它们是CSF1R、HGF、IGF2、ITGA6、MMP9、MMP11、MMP13、CASP8、CTSD、TMPRSS4、THBS2、TIMP1、ENPP2、SNCG。通过在DAVID生物信息学数据库中对上述表达差异显著的基因进行通路分析,结果提示差异基因主要富集在5条信号通路上,分别是肿瘤信号通路(MDM2、CASP8、CSF1R、HGF、ITGA6、LAMC1、MMP9、PTGS2)、ECM受体整合信号通路(LAMC1、THBS、ITGA6)、基质金属蛋白酶信号通路(TIMP1、MMP9)、小细胞肺癌信号通路(ITGA6、Cox2)和黏着斑信号通路(ITGA6、HGF、IGF2)。结论 MTA1参与了转移相关的一系列分子改变事件,尚需进一步的分子生物学方法验证这些基因调控的信号途径。
Objective To investigate the effect of MTA1 on esophageal cancer metastasis-related genes. Methods The RNA interference method was used to silence the expression of MTA1 gene in esophageal cancer cell line KYSE150, and then the metastasis - associated gene chip analysis was performed. Two-fold increase in the two chip analysis (or down 1/2) were significantly different genes. Pathology analysis of gene ontology by DIVID bioinformatics database. Results There were 7 genes that were up-regulated in the two microarray analyzes, including LAMC1, MMP14, MMP15, MDM2, API5, ODC1 and PTGS2, respectively. HGF, IGF2, ITGA6, MMP9, MMP11, MMP13, CASP8, CTSD, TMPRSS4, THBS2, TIMP1, ENPP2, SNCG. Pathway analysis of these genes with significant differences in expression in the database of Bioinformatics in DAVID indicated that the differential genes were mainly enriched in five signal pathways including tumor signal pathways (MDM2, CASP8, CSF1R, HGF, ITGA6, LAMC1 , MMP9, PTGS2), ECM receptor integrated signal pathway (LAMC1, THBS, ITGA6), matrix metalloproteinase pathway (TIMP1, MMP9), small cell lung cancer signal pathway (ITGA6, Cox2) and focal adhesion signal pathway , IGF2). Conclusions MTA1 is involved in a series of molecular changes related to metastasis. Further molecular biological methods are needed to validate the signaling pathways regulated by these genes.