MicroRNA expression patterns and target prediction in multiple myeloma development and malignancy.
MicroRNA expression patterns and target prediction in multiple myeloma development and malignancy.
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DOI：
10.1007/s13258-017-0518-7
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发表时间：
2017
期刊：
影响因子：
2.1
通讯作者：
Zakaria Z
中科院分区：
文献类型：
--
作者：
Bong IPN;Ng CC;Baharuddin P;Zakaria Z
表观遗传学改变已成为多发性骨髓瘤(MM)发生和发展的关键原因。本研究采用基因芯片技术对27例MM(19例标本和8个细胞系)和3例正常对照进行了miRNA表达谱分析。通过整合miRNA表达谱和匹配样本的mRNA表达谱(未发表的数据)来识别miRNA靶标。选择两个miRNAs进行RT-qPCR验证(miR-150-5P和miR-4430)。与对照组相比，MM组共有1791个≥过度表达，8个miRNA低表达(Folge Change miRNA 2.0；p <； 0.05)。5个可能的靶基因(RAD54L、CcNA2、CySLTR2、RASGRF2和HKDc1)与15个miRNAs(p <； 0.0 5)呈负相关。大多数差异表达的miRNAs与MM的生存、增殖、迁移、侵袭和耐药有关，其中一些从未与MM相关(miR-33a、miR-9和miR-211)。有趣的是，我们的结果发现了两个与B细胞分化密切相关的miRNAs(miR-150和miR-125b)。我们首次认为miR-150可能是两个关键的细胞周期控制基因RAD54L和Ccna2的潜在负调控基因，而miR-125b可能分别针对Ras和CysLT信号蛋白，即RASGRF2和CySLTR2。本研究加深了我们对多发性骨髓瘤病理生物学的认识，为今后骨髓增多症的研究开辟了新的途径。本文的在线版本(doi：10.1007/s13258-0170518-7)包含补充材料，授权用户可以使用。
Epigenetic changes have emerged as key causes in the development and progression of multiple myeloma (MM). In this study, global microRNA (miRNA) expression profiling were performed for 27 MM (19 specimens and 8 cell lines) and 3 normal controls by microarray. miRNA-targets were identified by integrating the miRNA expression profiles with mRNA expression profiles of the matched samples (unpublished data). Two miRNAs were selected for verification by RT-qPCR (miR-150-5p and miR-4430). A total of 1791 and 8 miRNAs were over-expressed and under-expressed, respectively in MM compared to the controls (fold change ≥2.0; p < 0.05). The miRNA-mRNA integrative analysis revealed inverse correlation between 5 putative target genes (RAD54L, CCNA2, CYSLTR2, RASGRF2 and HKDC1) and 15 miRNAs (p < 0.05). Most of the differentially expressed miRNAs are involved in survival, proliferation, migration, invasion and drug resistance in MM. Some have never been described in association with MM (miR-33a, miR-9 and miR-211). Interestingly, our results revealed 2 miRNAs, which are closely related to B cell differentiation (miR-150 and miR-125b). For the first time, we suggest that miR-150 might be potential negative regulator for two critical cell cycle control genes, RAD54L and CCNA2, whereas miR-125b potentially target RAS and CysLT signaling proteins, namely RASGRF2 and CYSLTR2, respectively. This study has enhanced our understanding on the pathobiology of MM and opens up new avenues for future research in myelomagenesis. The online version of this article (doi:10.1007/s13258-017-0518-7) contains supplementary material, which is available to authorized users.