基于microRNA差异表达探讨恶性纤维组织细胞瘤致病机制

目的 应用芯片表达分析技术探讨miRNA在恶性纤维组织细胞瘤发病机制中的作用.方法 利用miRCURYTM LNA miRNA表达谱芯片技术高通量筛选NMFH1与MSC、HSF、MRC-5和HT-1080细胞系差异表达miRNA,筛选靶基因,分析调控作用机制.结果 筛查NMFH1与4种对照组细胞系差异表达miRNA,选取与所有正常样本对比均下调miR-222、miR-186及miR-933,均上调miR-886-3p、miR-886-5p、miR-183、miR-340及miR-BART7进行qRT-PCR实验,验证芯片数据可靠性.基于生物信息学方法挖掘miRNA靶基因,构建基因调控网络,基于功能组注释信息分析NMFH1风险疾病基因及通路,揭示MFH恶性病变机制.结论 miRNA在肿瘤样本与正常细胞系间显著差异表达,是参与MFH发生发展过程的重要调控因子,发挥负调控基因表达作用,使肿瘤细胞逃避正常生长调控机制,无限增殖和转移,出现恶性表型.

Identifying pathogenic mechanism of malignant fibrous histiocytoma based on differential expression of microRNA

Objective To investigate the differential expression of microRNA in MFH by miRNA array technique. Methods A high throughput MiRCURYTM LNA miRNA array was applied to identify the microRNAs with differential expression in the novel MFH cell （NMFH） in comparison with 4 control cell lines including ＇embryonic lung fihroblast （ MRC-5 ） , mesenchymal stem cell （ MSC ） , human skin fibrous （HSF） and fibrosarcoma （ HT-1080 ） cell. Results Three down-regulated miR-222, miR-186, miR - 933 and five up - regulated miR- 886 - 3 p, miR- 886 - 5 p, miR - 183, miR - 340, miR- BART7 were picked for qRT-PCR validation based on their expression level changes and their similar status in the 4 control cell lines. Potential target genes of these miRNA, their regulated networks, the disease associated genes and pathways were analyzed by bioinformatic methods in combination with functional annotation. Condusion Differential expression of miRNAs in the tumor cells, is an important regulatory factor in the occurrence and development of MFH. It makes the tumor cells escape the normal growth regulation, and become malignant with capacity of unlimited proliferation and metastasis.