【摘要】 目的: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靶基因及其功能,为进一步研究miR-550a-5p及其靶基因在MDS发病机制中的作用提供依据。方法:采用realtime PCR技术检测miR-550a-5p在54例MDS患者、16例MDS转化白血病患者及19例健康对照中的表达量,并分析其与临床病理特征（包括染色体情况、骨髓原始细胞比例及外周血血象）的相关性。应用miRBase获得并分析多个物种miR-550的序列特征;应用Microcosm、Miranda和Targetscan预测miR-550a-5p的靶基因,并取预测结果交集,进一步进行基因功能的GO（富集）分析和信号转导通路（Pathway）的富集分析。结果:miR-550a-5p表达量在所有MDS患者骨髓中均比对照组升高:在低危+中危1组中表达量是对照组的1.7倍（P=1.23×10-10）;在中危2+高危组中表达量是对照组的1.9倍(P=1.20×10^-10);在MDS转化为白血病组中的表达量是对照组的2.0倍(P=5.61×10^-10)。随着MDS疾病危险度增高,miR-550a-5p表达水平逐渐上升,但其表达量与MDS患者的临床病理特征（包括染色体情况、骨髓原始细胞比例及外周血血象）之间无明显相关。利用生物信息学预测miR-550a-5p在MDS中的靶基因,结合文献报道选出了其中2个可能与miR-550a-5p调控MDS发生发展的病理机制有关的靶基因——PDLIM2和PSME1。结论:miR-550a-5p在MDS患者骨髓细胞中呈现出特异性高表达,推测其可能通过调控靶基因PDLIM2和PSME1参与MDS病理生理过程。更多还原

【Abstract】 Objective: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.Methods: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.Results: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^-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^-10);the expression of miR-550a-5p in tAML was 2.0 times of controls(P=5.61×10^-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.Conclusion: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.更多还原