摘要
目的 筛选和分析苯作业工人血浆差异表达微小RNA（micro RNA,miRNA）,探讨血浆miRNAs在苯引起工人血液毒性中的潜在作用.方法 采用个体匹配方式选取血细胞降低、血细胞波动以及正常接苯工人各10人,利用微阵列芯片检测3组工人血浆差异表达miRNAs,用实时荧光定量聚合酶链反应技术（real-time quantitative polymerase chain reaction,RT-qPCR）进行验证,用Targetscan、Pictar及miRanda等3个软件预测9个差异显著且信号值较大的miRNAs的潜在靶基因,然后利用David 6.7在线平台作基因本体论（GO）分析和全基因组及代谢途径数据库（KEGG）通路分析.结果 根据微阵列芯片结果,发现138个差异表达的miRNAs,聚类分析结果显示差异表达miRNAs中有三类比较显著的表达模式.RT-qPCR结果显示,miR-638、let-7f-5p及miR-223-3p芯片表达水平与RT-qPCR验证结果比较一致.通路分析表明富集程度最高的是黏着斑通路（focal adhesion）,包括SOS2、VCL、CCND2、COL4A6、IGF1和MAPK1等6个潜在功能靶点.结论 利用微阵列芯片初步筛选出苯作业工人血浆miRNA表达谱,生物信息学分析提示黏着斑通路与苯血液毒性有关.
Objective To find out and analyze differentially expressed miRNAs in the plasma of benzene exposed workers,and explore the potential roles of plasma miRNAs in the development of hematologic toxicity induced by benzene exposure.Methods By individual matching,low blood cell group,unstable blood cell group and normal group of 10 benzene exposed workers in each group were taken as subjects.Microarray was used to find out differentially expressed miRNAs among three groups.Three miRNAs validated by real-time quantitative PCR.Target genes of 9 miRNAs with the high abundance and significant difference were predicted using Targetscan,Pictar and miRanda softwares.David 6.7 online platform was used to perform GO term enrichment and KEGG pathway analysis of those targets.Results Microarray screened out that 138 miRNAs were differentially expressed.Three significant classes of differentially expressed miRNAs were found with the cluster analysis.The detected expressions of miR-638,let-7f-5p and miR-223-3p by relative RT-qPCR was consistent with the microarray date.Pathway analysis showed that the most enriched pathway was focal adhesion,with 6 potential functional targets,including SOS2,VCL,CCND2,COL4A6,IGF1 and MAPK1.Conclusion We have identified the plasma miRNA profile in benzene exposed workers,and further analysis indicates that focal adhesion-associated miRNAs play a potential role in hematologic toxicity induced by benzene exposure.
出处
《中华劳动卫生职业病杂志》
CAS
CSCD
北大核心
2014年第7期511-515,共5页
Chinese Journal of Industrial Hygiene and Occupational Diseases
基金
卫生部卫生行业科研专项（200902006）
江苏省医学创新团队与领军人才项目（LJ201130）
关键词
苯
职业暴露
血浆
微小RNA
Benzene
Occupational exposure
Plasma
MicoRNA
