Xiang Tian, Hu Ai-Xin, Sun Peng, Liu Gao, Liu Gang, Xiao Yan
Department of Clinical Laboratory Center, Central Hospital of Enshi Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, Hubei, China.
The Department of Orthopedic Surgery, People's Hospital of Three Gorges University, YiChang, Hubei, China.
PeerJ. 2017 Jan 31;5:e2831. doi: 10.7717/peerj.2831. eCollection 2017.
Multiple myeloma is a cancer which has a high occurrence rate and causes great injury to people worldwide. In recent years, many studies reported the effects of miRNA on the appearance of multiple myeloma. However, due to the differences of samples and sequencing platforms, a large number of inconsistent results have been generated among these studies, which limited the cure of multiple myeloma at the miRNA level.
We performed meta-analyses to identify the key miRNA biomarkers which could be applied on the treatment of multiple myeloma. The key miRNAs were determined by overlap comparisons of seven datasets in multiple myeloma. Then, the target genes for key miRNAs were predicted by the software TargetScan. Additionally, functional enrichments and binding TFs were investigated by DAVID database and Tfacts database, respectively.
Firstly, comparing the normal tissues, 13 miRNAs were differently expressed miRNAs (DEMs) for at least three datasets. They were considered as key miRNAs, with 12 up-regulated (hsa-miR-106b, hsa-miR-125b, hsa-miR-130b, hsa-miR-138, hsa-miR-15b, hsa-miR-181a, hsa-miR-183, hsa-miR-191, hsa-miR-19a, hsa-miR-20a, hsa-miR-221 and hsa-miR-25) and one down-regulated (hsa-miR-223). Secondly, functional enrichment analyses indicated that target genes of the upregulated miRNAs were mainly transcript factors and enriched in transcription regulation. Besides, these genes were enriched in multiple pathways: the cancer signal pathway, insulin signal metabolic pathway, cell binding molecules, melanin generation, long-term regression and P53 signaling pathway. However, no significant enrichment was found for target genes of the down-regulated genes. Due to the distinct regulation function, four miRNAs (hsa-miR-19a has-miR-221 has-miR25 and has-miR223) were ascertained as the potential prognostic and diagnostic markers in MM. Thirdly, transcript factors analysis unveiled that there were 148 TFs and 60 TFs which bind target genes of the up-regulated miRNAs and target genes of the down-regulated miRNAs, respectively. They respectively generated 652 and 139 reactions of TFs and target genes. Additionally, 50 (31.6%) TFs were shared, while higher specificity was found in TFs of target genes for the upregulated miRNAs.
Together, our findings provided the key miRNAs which affected occurrence of multiple myeloma and regulation function of these miRNAs. It is valuable for the prognosis and diagnosis of multiple myeloma.
多发性骨髓瘤是一种发病率很高且对全球人们造成巨大伤害的癌症。近年来，许多研究报道了微小RNA（miRNA）对多发性骨髓瘤发生的影响。然而，由于样本和测序平台的差异，这些研究产生了大量不一致的结果，这限制了在miRNA水平上对多发性骨髓瘤的治疗。
我们进行了荟萃分析，以确定可应用于多发性骨髓瘤治疗的关键miRNA生物标志物。通过对多发性骨髓瘤的七个数据集进行重叠比较来确定关键miRNA。然后，使用TargetScan软件预测关键miRNA的靶基因。此外，分别通过DAVID数据库和Tfacts数据库研究功能富集和结合转录因子。
首先，与正常组织相比，至少在三个数据集中有13种miRNA是差异表达的miRNA（DEM）。它们被视为关键miRNA，其中12种上调（hsa-miR-106b、hsa-miR-125b、hsa-miR-130b、hsa-miR-138、hsa-miR-15b、hsa-miR-181a、hsa-miR-183、hsa-miR-191、hsa-miR-19a、hsa-miR-20a、hsa-miR-221和hsa-miR-25），一种下调（hsa-miR-223）。其次，功能富集分析表明上调miRNA的靶基因主要是转录因子，并且富集于转录调控。此外，这些基因富集于多种途径：癌症信号通路、胰岛素信号代谢通路、细胞结合分子、黑色素生成、长期回归和P53信号通路。然而，下调基因的靶基因未发现明显富集。由于具有独特的调控功能，四种miRNA（hsa-miR-19a、hsa-miR-221、hsa-miR-25和hsa-miR-223）被确定为多发性骨髓瘤潜在的预后和诊断标志物。第三，转录因子分析表明分别有148个和60个转录因子与上调miRNA的靶基因和下调miRNA的靶基因结合。它们分别产生了652个和139个转录因子与靶基因的反应。此外，有50个（31.6%）转录因子是共享的，而上调miRNA靶基因的转录因子具有更高的特异性。
总之，我们的研究结果提供了影响多发性骨髓瘤发生的关键miRNA以及这些miRNA的调控功能。这对多发性骨髓瘤的预后和诊断具有重要价值。
