南方医科大学学报

南方医科大学学报 ›› 2018, Vol. 38 ›› Issue (10): 1151-.doi: 10.12122/j.issn.1673-4254.2018.10.01

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KIAA0101调控胃癌细胞周期的相关基因筛选

王直，党诚学，闫融，张昊，袁达伟，李康   

  • 出版日期:2018-10-20 发布日期:2018-10-20

Screening of cell cycle-related genes regulated by KIAA0101 in gastric cancer

  • Online:2018-10-20 Published:2018-10-20

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摘要： 目的筛选KIAA0101 基因对细胞周期影响的相关基因。方法以RT-PCR方法分析胃癌组织相对于配对癌旁组织中 KIAA0101基因表达量，利用DAVID数据库对差异基因进行GO功能富集分析和KEGG通路富集分析，使用KEGG绘制通路 图，将与KIAA0101表达模式相关的基因列表回带入TCGA cBioPortal进行基因之间相互网络作用的关系研究，并借由系统生 成基因拓扑关系图。最后采用RT-PCR方法对候选基因进行筛选。结果癌组织中KIAA0101 mRNA表达水平为1.104±0.379， 显著高于配对癌旁组织（0.421±0.172；P=0.0179）。系统通过汇总分析全部基因探针的表达强度，对来自478 例组织中与 KIAA0101相关的基因进行了筛选。GO功能分析显示差异基因主要富集在蛋白磷酸化、RNA加工、细胞周期、DNA代谢过程、 蛋白质转运、乙酰化、细胞凋亡、蛋白质水解、氧化还原等功能。KIAA0101表达水平的改变主要影响的胃癌相关通路有：细胞周 期、剪接体、DNA复制、p53 信号转导通路等。KEGG通路图及基因拓扑图显示，BUB1B、MAD2L1、CDC45、CDK1、CCNE1、 CCNB2等与KIAA0101相关的基因也与细胞周期相关，RT-PCR结果证实BUB1B、MAD2L、CDK1、CCNE1、CCNB2 mRNA表 达水平显著高于配对癌旁组织（P<0.05），CDC45 mRNA表达水平无显著性差异（P>0.05）。结论KIAA0101 可能通过影响 BUB1B、MAD2L1、CDK1、CCNE1、CCNB2 表达产生对细胞周期的影响，这个结果可以为KIAA0101 影响细胞周期的作用机 制、肿瘤标志物的筛选和药物靶点的选择提供参考。

Abstract: Objective To screen the genes related to cell cycle under regulation by KIAA0101 in gastric cancer. Methods RT-PCR was used to detect the expression level of KIAA0101 gene in gastric cancer tissue and paired adjacent tissues. GO function enrichment analysis and KEGG pathway enrichment analysis were carried out using DAVID database. KEGG was used to map the pathways and the corresponding genes were analyzed. The list of genes associated with the KIAA0101 expression pattern was imported into TCGA cBioPortal to analyze the relationship between the interacting genes and generate a genetic topology map. The candidate genes were screened by RT-PCR. Results The expression level of KIAA0101 mRNA was significantly higher in cancer tissues than in paired adjacent tissues (1.104 ± 0.379 vs 0.421 ± 0.172; P=0.0179). The system screened genes related with KIAA0101 from 478 tissues by pooled analysis of the expression intensity of all the gene probes. GO function analysis showed that the differential genes were mainly enriched in protein phosphorylation, RNA processing, cell cycle, DNA metabolism, protein transport, acetylation, apoptosis, proteolysis, and redox. The changes in the expression level of KIAA0101 mainly affect the gastric cancer-related pathways including cell cycle, spliceosome, DNA replication, and p53 signal transduction pathway. KEGG pathway maps and gene topology maps showed that the genes related to KIAA0101 (such as BUB1B, MAD2L1, CDC45, CDK1, CCNE1 and CCNB2) were also related to cell cycle. RT-PCR results confirmed significant increments of the expression levels of BUB1B, MAD2L, CDK1, CCNE1, and CCNB2 mRNA in gastric cancer tissues as compared with the paired adjacent gastric tissues (P<0.05), but CDC45 mRNA did not show significant differential expression in gastric cancer tissues (P>0.05). Conclusion KIAA0101 may affect cell cycle by regulating the expression of BUB1B, MAD2L1, CDK1, CCNE1 and CCNB2, and this finding may provide evidence for understanding how KIAA0101 affects cell cycle and for screening of tumor markers and selection of drug targets.