Huang Ying, Wen Jing, Li Hong-Ying, Zhang Xu-Pai, Deng Dong-Hong, Cheng Peng, Peng Zhi-Gang, Zhao Wei-Hua, Luo Jun, Long Yuan, Liu Zheng-Fang
Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China. E-mail:
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2016 Oct;24(5):1476-1483. doi: 10.7534/j.issn.1009-2137.2016.05.035.
To investigate the expression of miR-550a-5p in bone marrow of patients with myelodysplastic syndrome (MDS), and to predict its target genes and function by bioinformatics analyses, so as to provide the evidence to furthre explore the role of miR-550a-5p and its target genes in pathogenesis of MDS.
Real-time PCR was used to detect the expression of miR-550a-5p in 54 MDS patients, 16 acute myeloid leukemia transformed from MDS (sfAML) and 19 healthy controls, and the correlation between the expression of miR-550a-5p and clinical pathologic characteristics of MDS, including chromosome, percentage of marrow blasts, absolute neutrophil count, platelet count and hemoglobin levels were analyzed. The sequence of miR-550 was searched in miRBase database. Target genes of miR-550a-5p were predicted by Microcosm,Miranda and Targetscan, and the predective results were collected, then the enrichment analyses of target gene function(GO) and signalling pathway(pathway of miR-550a-5p) were carried out by using gene ontology darabase and KEGG database.
The expression of miR-550a-5p in bone marrow of all MDS patients was higher than that in controls: the expression level of miR-550a-5p in low risk MDS and middl risk 1 MDS was 1.7 times of controls (P=1.23×10); the expression of miR-550a-5p in midde risk 2 MDS and high risk MDS was 1.9 times of controls (P=1.20×10); the expression of miR-550a-5p in tAML was 2.0 times of controls (P=5.61×10). The miR-550a-5p expression level was up-regulated gradually with the enhancement of disease risk of MDS, but there was no correlation between the expression level of miR-550a-5p and clinical pathologic characteristics of MDS(chromosome: Normal: 1.11±0.19, Abnormal:1.26±0.15, P>0.05; Percentage of Marrow Blasts: r=0.29,P=0.07; absolute neutrophil count: r=-0.02,P=0.89; hemoglobin level: r=0.09,P=0.57; platelet count: r=0.25,P=0.08). The sequence of miR-550 was conservative among different species, and the prediced results indicated that there were 19 target genes in intersection. The functions of target genes were enriched in regulation of stress-activated cascade, MAPK pathway, regulation of muscle organ development, regulation of protein homodimerization activity and other biological processes; they participated in some molecular functions including enzyme activity, combination processes of some molecules as protein, cAMP and domain existed in cell junction, synapse, coated vesicle, dendrite and other cellular components. Two of them-PDLIM2 and PSME1 were selected which might play a role in pathologic mechanism of MDS regulated by miR-550a-5p.
The expression of miR-550a-5p in bone marrow of MDS patients increases specifically, and miR-550a-5p may play a role in the pathogenesis of MDS through regulation of target genes, PDLIM2 and PSME1.
探讨miR-550a-5p在骨髓增生异常综合征（MDS）患者骨髓中的表达情况，并通过生物信息学分析预测其靶基因及功能，为进一步探究miR-550a-5p及其靶基因在MDS发病机制中的作用提供依据。
采用实时荧光定量PCR检测54例MDS患者、16例MDS转化的急性髓系白血病（sfAML）患者及19例健康对照者骨髓中miR-550a-5p的表达，并分析miR-550a-5p表达与MDS临床病理特征（包括染色体、骨髓原始细胞百分比、中性粒细胞绝对值、血小板计数及血红蛋白水平）之间的相关性。在miRBase数据库中检索miR-550的序列。利用Microcosm、Miranda和Targetscan预测miR-550a-5p的靶基因，收集预测结果，然后使用基因本体数据库和KEGG数据库对靶基因功能（GO）及信号通路（miR-550a-5p的通路）进行富集分析。
所有MDS患者骨髓中miR-550a-5p的表达均高于对照组：低危MDS和中危1 MDS中miR-550a-5p的表达水平是对照组的1.7倍（P=1.23×10）；中危2 MDS和高危MDS中miR-550a-5p的表达是对照组的1.9倍（P=1.20×10）；tAML中miR-550a-5p的表达是对照组的2.0倍（P=5.61×10）。miR-550a-5p表达水平随MDS疾病风险的增加而逐渐上调，但miR-550a-5p表达水平与MDS临床病理特征之间无相关性（染色体：正常：1.11±0.19，异常：1.26±0.
