中国癌症杂志 ›› 2016, Vol. 26 ›› Issue (11): 916-921.doi: 10.19401/j.cnki.1007-3639.2016.11.006

• 论著 • 上一篇    下一篇

肠炎和肠炎相关结直肠癌miRNA表达检测及生物信息学分析

殷 媛1,王 成2,戴 欣3,黄朝晖1   

  1. 1. 江南大学附属医院肿瘤研究所,江苏 无锡 214062 ;
    2. 南京军区南京总医院检验科,江苏 南京 210002 ;
    3. 美世大学药学院,制药科学系,癌症纳米医学实验室,佐治亚州 亚特兰大 30341
  • 出版日期:2016-11-30 发布日期:2017-01-22
  • 通信作者: 黄朝晖 E-mail: hzhwxsy@126.com
  • 基金资助:
    国家自然科学基金(81301784,81272299,81000867)。

Investigation of key miRNAs and their target genes in inflammatory bowel diseases and colitisassociated colorectal cancers using miRNA profiling and bioinformatic tools

YIN Yuan1, WANG Cheng2, DAI Xin3, HUANG Zhaohui1   

  1. 1. Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu Province, China; 2. Department of Clinical Laboratory, Nanjing General Hospital of Nanjing Military Command, PLA, Nanjing 210002, Jiangsu Province, China; 3. Cancer Nanomedicine Laboratory, Department of Pharmaceutical Sciences, Mercer University College of Pharmacy, Atlanta 30341, GA, USA
  • Published:2016-11-30 Online:2017-01-22
  • Contact: HUANG Zhaohui E-mail: hzhwxsy@126.com

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(miRNA)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miRNAs进行靶基因归集和生物信息学分析,为以miRNAs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miRNAs的表达。通过生物信息学对显著变化的一组miRNA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miR-146a和癌症相关miR-27a、miR-29a、miR-20a、miR-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miRNA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:miR-146a、miR-27a、miR-29a、miR-20a和miR-21可能是参与肠炎向结直肠癌转化的一组miRNA。

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应, GO分析, KEGG分析, BIOCARTA分析

Abstract: 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 ageand 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 immunity-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.

Key words: miRNA, Ulcerative colitis, Crohn’s disease, Colitis-associated colorectal cancers, Real-time fluorescent quantitative polymerase chain reaction, GO-analysis, KEGG-analysis, BIOCARTA-analysis