An in silico analysis of dynamic changes in microRNA expression profiles in stepwise development of nasopharyngeal carcinoma

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• 作者：Zhaohui Luo (1)
  Liyang Zhang (1)
  Zheng Li (1)
  Xiayu Li (1)
  Gang Li (2)
  Haibo Yu (1)
  Chen Jiang (1)
  Yafei Dai (1)
  Xiaofang Guo (1)
  Juanjuan Xiang (1)
  Guiyuan Li (1)
  
• 刊名：BMC Medical Genomics
• 出版年：2012
• 出版时间：December 2012
• 年：2012
• 卷：5
• 期：1
• 全文大小：995KB
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  50. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1755-8794/5/3/prepub
  
• 作者单位：Zhaohui Luo (1)
  Liyang Zhang (1)
  Zheng Li (1)
  Xiayu Li (1)
  Gang Li (2)
  Haibo Yu (1)
  Chen Jiang (1)
  Yafei Dai (1)
  Xiaofang Guo (1)
  Juanjuan Xiang (1)
  Guiyuan Li (1)
  
  1. Cancer Research Institute, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Carcinogenesis of Ministry of Health, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, P.R. China
  2. The Li Ka Shing Institute of Health Sciences, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong
  
• ISSN：1755-8794

文摘

Background MicroRNAs (miRNAs) are small non-coding RNAs that participate in the spatiotemporal regulation of messenger RNA (mRNA) and protein synthesis. Recent studies have shown that some miRNAs are involved in the progression of nasopharyngeal carcinoma (NPC). However, the aberrant miRNAs implicated in different clinical stages of NPC remain unknown and their functions have not been systematically studied. Methods In this study, miRNA microarray assay was performed on biopsies from different clinical stages of NPC. TargetScan was used to predict the target genes of the miRNAs. The target gene list was narrowed down by searching the data from the UniGene database to identify the nasopharyngeal-specific genes. The data reduction strategy was used to overlay with nasopharyngeal-specifically expressed miRNA target genes and complementary DNA (cDNA) expression data. The selected target genes were analyzed in the Gene Ontology (GO) biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway. The microRNA-Gene-Network was build based on the interactions of miRNAs and target genes. miRNA promoters were analyzed for the transcription factor (TF) binding sites. UCSC Genome database was used to construct the TF-miRNAs interaction networks. Results Forty-eight miRNAs with significant change were obtained by Multi-Class Dif. The most enriched GO terms in the predicted target genes of miRNA were cell proliferation, cell migration and cell matrix adhesion. KEGG analysis showed that target genes were significantly involved in adherens junction, cell adhesion molecules, p53 signalling pathway et al. Comprehensive analysis of the coordinate expression of miRNAs and mRNAs reveals that miR-29a/c, miR-34b, miR-34c-3p, miR-34c-5p, miR-429, miR-203, miR-222, miR-1/206, miR-141, miR-18a/b, miR-544, miR-205 and miR-149 may play important roles on the development of NPC. We proposed an integrative strategy for identifying the miRNA-mRNA regulatory modules and TF-miRNA regulatory networks. TF including ETS2, MYB, Sp1, KLF6, NFE2, PCBP1 and TMEM54 exert regulatory functions on the miRNA expression. Conclusions This study provides perspective on the microRNA expression during the development of NPC. It revealed the global trends in miRNA interactome in NPC. It concluded that miRNAs might play important regulatory roles through the target genes and transcription factors in the stepwise development of NPC.