[Bioinformatics analysis of microRNA comprehensive regulatory network in B- cell acute lymphoblastic leukemia]

Zhonghua Xue Ye Xue Za Zhi. 2016 Jul;37(7):585-90. doi: 10.3760/cma.j.issn.0253-2727.2016.07.009.
[Article in Chinese]

Abstract

Objective: To reveal the involvement of molecules in the pathogenesis of B-cell acute lymphoblastic leukemia (B-ALL) by bioinformatics analyses.

Methods: The microarray data of B-ALL were downloaded from the Gene Expression Omnibus (GEO) database and Qlucore Omics Explorer software was used to screen differentially expressed miRNA. Based on the differentially expressed miRNAs, we predicted the target genes, long non-coding RNAs (lncRNA) and transcription factors (TFs). Then we constructed the miRNAs-centered comprehensive regulatory network. In addition, we performed functional enrichment analysis to analyze the functions of target genes.

Results: Of all the 15 differentially expressed miRNAs, 7 miRNAs were of overexpression, 8 miRNAs underexpressed. From the miRNAs comprehensive regulatory network, we found that hsa-miR-486-3p and hsa-miR-126 regulated a large number of target genes, hsa-miR-126 including target genes MYC. The hsa-miR-29a, hsa-miR-130a and hsa-miR-181c regu- lated a lot of lncRNAs containing X-inactive-specific transcript (XIST). The hsa-miR-181a-2, hsa-miR- 181b-2 and hsa-miR-663 were regulated by a host of TFs including caudal- related homeobox transcription fact2 (CDX2). Additionally, the target genes of has-miR-126 were enriched in Wnt pathways.

Conclusions: The expression of hsa-miR-29a , hsa-miR-126 and has-miR-181 family were significantly different in B-ALL. Target gene of MYC, TFs of CDX2 and lncRNA of XIST may play important roles in the development of B-ALL, serving as a potential therapeutic target.

目的: 通过生物信息分析途径,从系统水平揭示参与急性B淋巴细胞白血病(B-ALL)发病的分子机制,为研究提供新的思路。

方法: 从公共数据库GEO中下载B-ALL的microRNA (miRNA)芯片数据,利用Qlucore Omics Explorer 3. 0软件筛选差异表达miRNA,再分析得到差异miRNA与靶基因、长链非编码RNA和转录因子各自的调控数据,然后构建以差异miRNA为中心的综合调控网络。另外,功能富集分析有功能的靶基因。

结果: 共筛选出15个差异miRNA,其中7个miRNA表达上调,8个miRNA表达下调。通过差异miRNA为中心的综合调控网络可知,hsa-miR-126和hsa-miR-486-3p调控大量的靶基因,其中hsa-miR-126的靶基因包括MYC基因。hsa-miR-29a、hsa-miR-130a和hsa-miR-181c调控大量的长链非编码RNA,包括XIST。hsa-miR-181a-2、hsa-miR-181b-2和hsa-miR-663调控大量的转录因子,包括CDX2、YY1等。hsa-miR-126靶基因的通路分析显示富集到Wnt通路。

结论: 通过生物信息学方法分析得出,hsa-miR-29a、hsa-miR-126和hsa-miR-181家族是B-ALL的核心差异miRNA,及其转录因子CDX2、长链非编码RNA XIST和靶基因MYC基因在B-ALL的发生发展中起重要作用,可能为潜在的治疗靶点。

MeSH terms

  • Computational Biology
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks*
  • Humans
  • MicroRNAs / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • RNA, Long Noncoding / genetics
  • Transcription Factors / genetics

Substances

  • MIRN126 microRNA, human
  • MIRN29 microRNA, human
  • MIRN486 microRNA, human
  • MIRN663 microRNA, human
  • MIrn181 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Transcription Factors

Grant support

基金项目:国家自然科学基金(39880032);广东省领军人才基金(C1030925)