目的利用生物信息学方法预测miR-210的红细胞系(以下简称红系)相关下游靶基因。方法利用NCBI比对分析miR-210成熟序列在各哺乳动物之间的保守性。运用基因数据库筛选miR-210的下游靶基因。采用Cytoscape中的BINGO插件对预测的miR-210下游靶基因进行GO分类富集分析。筛选参与红系增殖、分化、凋亡的miR-210下游靶基因,采用DAVID和KEGG数据库进行信号转导通路富集分析后,预测miR-210的红系相关下游靶基因。利用Targetscan在线工具验证靶基因与miR-210的相互作用关系。结果 miR-210成熟序列在多物种间具有高度保守性。筛选出416个与miR-210相关性较高的预测靶基因,其分子功能集中在蛋白结合、离子跨膜运输活动、酶结合等,参与的生物学过程集中在细胞信号转导、突触传导等,参与构成的细胞组分主要有突触小泡、细胞质、细胞器等。筛选出26个与红系增殖、分化、凋亡密切相关的miR-210下游靶基因,参与调控的信号通路主要集中于癌症信号通路、PI3K-Akt信号通路等。初步确定Smad3、Mapk10、Stat5a、Ywhag、Ctgf、Kitl6基因与红系增殖、分化密切相关,其中Smad3、Mapk10、Stat5a、Ywhag、Kitl可能受miR-210的直接调控,Ctgf可能受miR-210的间接调控。结论初步筛选出miR-210的红系相关下游靶基因Smad3、Mapk10、Stat5a、Ywhag、Ctgf、Kitl6,这些靶基因可能与红系的增殖、分化有关。
Objective To predict the downstream target genes related to miR-210 erythroid cells by bioinformatics.Methods NCBI was used to analyze the conservation of the mature sequence of miR-210 in mammals. The online database of bioinformatics was applied to predict miR-210 downstream target genes. The predicted miR-210 downstream target genes were analyzed by GO classification and enrichment using the BINGO insert in Cytoscape. Screening miR-210 downstream target genes involved in erythroid proliferation,differentiation and apoptosis. The downstream target genes of miR-210 were predicted by DAVID and KEGG database after signal transduction pathway enrichment analysis. Targetscan online tools were used to verify the interaction of target genes with miR-210. Results There was a highly conserved nature of miR-210 mature sequence in many species. The number of the predicted target genes highly related to miR-210 was 416. The molecular functions of target genes were enriched in protein binding,transmembrane transport activity of ion,enzyme binding and other molecular functions. The biological process were mainly cell signal transduction,synaptic transmission,etc.,and the compositions of the cell components were synaptic vesicles,cytoplasm,organelles and so on. We screened 26 miR-210 downstream target genes which were closely related to erythroid proliferation,differentiation and apoptosis. The signal pathways involved in the regulation were mainly cancer signaling pathway,PI3K-Akt signaling pathway and so on. Smad3,Mapk10,Stat5 a,Ywhag,Ctgf and Kitl6 genes were closely related to erythroid proliferation and differentiation,during which,Smad3,Mapk10,Stat5 a,Ywhag and Kitl might be directly regulated by mir-210,and Ctgf might be indirectly regulated by miR-210.Conclusions Smad3,Mapk10,Stat5 a,Ywhag,Ctgf and Kitl6 are initially screened for the downstream target genes related to miR-210 erythroid cells. These target genes may be related to the erythroid proliferation and differentiation.