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目的构建Alport综合征(AS)与正常对照者(NC)诱导多能干细胞(i PSCs)新核糖核苷酸(novel microRNA)差异性表达谱,分析其靶基因功能。方法采用前期工作成功从尿肾状杆细胞诱导成的i PSCs,运用高通量测序平台获得AS与NC的差异性表达谱,使用靶基因预测软件Target Scan进行靶基因预测,靶基因与参考基因比较后,在候选靶基因找到显著富集的GO条目及KEGG通路。结果在AS与NC中发现49个有意义的差异性表达novel microRNAs,其中33个表达上调,16个表达下调。在GO靶基因富集分析中,靶基因主要富集于生物调节、生物新陈代谢、细胞组成、细胞信号传导、酶催化反应、分子转运等过程。在KEGG通路分析中,靶基因主要参与代谢通路、嘌呤代谢、癌症转录调节等过程。结论来源于AS与NC的i PSCs存在较大的差异性表达novel microRNA,其靶基因在分子功能、细胞组成、生物过程起着重要作用。这些差异性表达的novel mciroRNAs与靶基因可能是AS发病机制的潜在位点。
Objective To construct differential expression profiles of novel microRNAs in induced pluripotent stem cells (iPSCs) between Alport syndrome (AS) and normal controls (NCs) and analyze their target gene function. Methods The iPSCs induced by renal renal stem cells were successfully obtained in the previous work. The differential expression profiles of AS and NC were obtained by using high-throughput sequencing platform. The target genes were predicted by Target Scan software Target Scan. The target genes and reference genes After comparison, significant enriched GO entries and KEGG pathways were found in the candidate target genes. Results There were 49 significant differences in the expression of novel microRNAs in AS and NC, of which 33 were up-regulated and 16 down-regulated. In GO target gene enrichment analysis, the target genes are mainly enriched in biological regulation, biological metabolism, cell composition, cell signaling, enzyme catalysis, molecular transport and other processes. In the KEGG pathway analysis, the target genes are mainly involved in the metabolic pathway, purine metabolism, cancer transcriptional regulation and the like. Conclusion The iPSCs derived from AS and NC are highly expressed in novel microRNAs, and their target genes play an important role in molecular function, cell composition and biological processes. These differentially expressed novel mciroRNAs and target genes may be potential sites for the pathogenesis of AS.