伴13号染色体缺失的多发性骨髓瘤患者CD138^+细胞差异表达miRNAs的筛选

Differential expressions of microRNAs in the CD138^+ cells of multiple myeloma patients with deletion of chromosome 13

目的初步筛选伴13号染色体缺失的多发性骨髓瘤患者CD138+细胞差异表达显著的microRNAs(miRNAs)并探求其生物学功能。方法通过荧光原位杂交(FISH)实验从29例多发性骨髓瘤初治患者中筛选出13号染色体缺失和核型正常的多发性骨髓瘤患者各3例;应用miRNA芯片技术获得差异表达miRNAs,并进行实时定量PCR验证;应用在线软件预测差异miRNAs的潜在靶基因,并建立miRNAs与靶基因的调控网络。结果检测出5个在伴13号染色体缺失的多发性骨髓瘤患者CD138+细胞中差异表达的miRNAs,其中4个表达下调,1个表达上调;生物信息学分析显示,SMAD3基因位于miRNAs-靶基因调控网络的关键节点上。结论伴13号染色体缺失的多发性骨髓瘤患者CD138+细胞中存在特异性表达的miRNAs;SMAD3基因可能在该类型多发性骨髓瘤发病中发挥作用。

Objective To screen the differentially expressed microRNAs in the CD138 ＋ cells of multiple myeloma （MM） patients with deletion of chromosome 13 and explore the biological functions of them. Methods 3 cases with chromosome 13 deletion and another 3 with normal karyotype from 29 previously untreated multiple myeloma patients were screened by fluorescence in situ hybridization （FISH）. The miRNA microarray was used to detect the differential- ly expressed miRNAs, and the real-time PCR was used to verify the results. The potential target genes of the detected differentially expressed miRNAs were predicted by online software. Then the regulatory network of miRNAs and target genes was established. Results Five differentially expressed miRNAs were detected in the CD138 ＋ cells of MM patients with deletion of chromosome 13, of which four were down-regulated and one was up-regulated obviously. Bioinformatic analysis showed that SMAD3 was in the key node of the miRNA-target gene regulatory network. Conclusion The multiple myeloma patients with chromosome 13 deletion have their specifically expressed miRNAs. The gene of SMAD3 may play an important role in the pathogenesis of this type of disease.