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肠炎和肠炎相关结直肠癌miRNA表达检测及生物信息学分析 被引量:12

Investigation of key miRNAs and their target genes in inflammatory bowel diseases and colitisassociated colorectal cancers using miRNA profiling and bioinformatic tools
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摘要 背景与目的:炎症性肠病(inflammatory bowel diseases,IBD)为一组慢性肠道疾病,包括溃疡性结肠炎(ulcerative colitis,UC)与克罗恩病(Crohn’s disease,CD)。肠炎相关性结直肠癌(colitis-associated colorectal cancers,CAC)是由IBD癌化形成的一种恶性肿瘤。该研究通过检测UC、CD和CAC组织中相关微小核糖核酸(mi RNA)的水平,初步探讨其作为肠炎癌转化分子标志物的可能性,并对在肠炎和CAC中显著变化的一组mi RNAs进行靶基因归集和生物信息学分析,为以mi RNAs为靶点的基因治疗提供理论和实验基础。方法:采用实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction,RTFQ-PCR)技术,检测13例UC组织、3例CD患者组织、12例CAC组织及8例正常肠组织中16种mi RNAs的表达。通过生物信息学对显著变化的一组mi RNA进行靶基因分析,将文献中已报导的所有靶基因进行汇总,并利用DAVID数据库对靶基因进行功能富集分析(GO-analysis)和信号转导通路富集分析(KEGG-analysis,BIOCARTA-analysis)。结果:炎症相关mi R-146a和癌症相关mi R-27a、mi R-29a、mi R-20a、mi R-21在UC、CD和CAC中的表达都显著高于正常结肠组织,且这一组mi RNA的靶基因都富集在癌症相关通路、免疫信号相关通路和炎癌转换相关通路上。结论:mi R-146a、mi R-27a、mi R-29a、mi R-20a和mi R-21可能是参与肠炎向结直肠癌转化的一组mi RNA。 Background and purpose: Inflammatory bowel diseases (IBD) are a group of chronic intestinal diseases, including ulcerative colitis (UC) and Crohn's disease (CD). This study identified differentially expressed miRNAs in UC, CD and colitis-associated colorectal cancers (CAC) to explore their potential as novel molecular biomarkers. Methods: Tissue samples were taken from 13 UC patients, 3 CD patients, 12 CAC patients, and 8 age- and gender-matched healthy controls. The miRNA expressions were detected by real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) assay. Known targets of deregulated miRNAs were utilized using miRWalk 2.0 database, and subsequent bioinformatics analysis of these target genes was performed by DAVID software (GO-analysis, KEGG-analysis and BIOCARTA-analysis). Results: The data showed that miR-146a, miR-27a, miR-29a, miR-20a and miR-21 were upregulated in UC, CD and CAC tissues compared with normal control. Moreover, the target genes of these miRNAs were enriched in several key signal transduction pathways including cancer-related pathway and immu- nity-associated pathway. Conclusion: miR-146a, miR-27a, miR-29a, miR-20a and miR-21 may play important roles in the switching from IBD to CAC.
出处 《中国癌症杂志》 CAS CSCD 北大核心 2016年第11期916-921,共6页 China Oncology
基金 国家自然科学基金(81301784,81272299,81000867)
关键词 微小核糖核酸 溃疡性结肠炎 克罗恩病 肠炎相关结直肠癌 实时荧光定量聚合酶链反 GO分析 KEGG分析 BIOCARTA分析 miRNA Ulcerative colitis Crohn's disease Colitis-associated colorectal cancers Real-time fluo-rescent quantitative polymerase chain reaction GO-analysis KEGG-analysis BIOCARTA-analysis
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