脐带间充质干细胞对NB4白血病细胞基因组表达谱的影响

Genome-wide transcriptional profiling of NB4 leukemic cells affected by umbilical cord-derived mesenchymal stem cells

背景:间充质干细胞是体内微环境的重要组成部分且影响肿瘤细胞的多种生物学行为,间充质干细胞的潜在临床价值是近年来的研究热点。目的:通过基因芯片方法分析脐带间充质干细胞对急性早幼粒细胞白血病细胞系NB4细胞基因组表达谱的影响。方法:体外建立脐带间充质干细胞与急性早幼粒细胞白血病细胞系NB4细胞共培养体系,检测脐带间充质干细胞对NB4细胞增殖、凋亡和分化的影响,分别提取了NB4细胞单独培养组和NB4细胞+脐带间充质干细胞共培养组NB4细胞的mRNA并将其反转录为cDNA,两组分别标记荧光,做成探针并与基因芯片杂交,检测其荧光强度,分析两组基因表达谱的差异。结果与结论:(1)脐带间充质干细胞促进NB4细胞的增殖和分化并抑制其凋亡;(2)脐带间充质干细胞作用后的NB4细胞的基因表达谱中有530个基因上调和53个基因下调,与基因相关的功能和信号通路也在一定程度上受到了调节;(3)结果表明,脐带间充质干细胞通过改变肿瘤细胞内大量基因表达、基因功能及多种信号通路影响NB4细胞的生物学行为。

BACKGROUND:Mesenchymal stem cells(MSCs)are an important component of the in vivo microenvironment and act on multiple biological behaviors of tumor cells.The potential clinical value of MSCs has become an issue of concern in recent years.OBJECTIVE:To investigate the gene expression profiles of acute promyelocytic leukemia(APL)cell line NB4treated with umbilical cord-derived MSCs(UC-MSCs)using cDNA microarray.METHODS:In vitro co-culture system was constructed,and then cellular proliferation,apoptosis and differentiation status of NB4cells treated with UC-MSCs were evaluated.Two cDNA probes were prepared through reverse transcription from mRNA of NB4cells treated with or without UC-MSCs.The probes were labeled with fluorescence dyes individually,hybridized with cDNA microarray,and their fluorescent intensities were scanned.The genes were screened through the analysis of the difference in two gene expression profiles.RESULTS AND CONCLUSION:UC-MSCs promoted the proliferation and differentiation,while reduced the apoptosis of NB4cells.The analysis of gene expression profiles indicated that after co-culture with UC-MSCs,530genes were up-regulated and53genes were down-regulated.Accordingly,specific gene function and pathway signaling related were also regulated to some extent.Overall,UC-MSCs influence can major biological behaviors of NB4cells by changing expression of a large amount of genes,gene-related function and multiple intracellular signaling pathways.