急性B淋巴细胞白血病的差异microRNA综合调控网络的生物信息学分析

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

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QlucoreOmicsExplorer3．0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．18ib-2和hsa．miR-663调控大量的转录因子，包括CDX2、YYl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RNAXIST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。

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 soft- ware 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-eentered 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 comprehen- sive 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- 181 c regu- lated a lot of lncRNAs containing X-inactive-specific transcript （XIST）. The hsa-miR-181a-2, hsa-miR- 18 lb-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 develop- ment of B-ALL, serving as a potential therapeutic target.