Identification of micro RNAs and their target genes in Alport syndrome using deep sequencing of iPSCs samples

运用高通量测序研究Alport综合征多能干细胞的microRNA及其靶基因(英文)

MicroRNAs （miRNAs） are a class of small RNA molecules that are implicated in post-transcriptional reg- ulation of gene expression during development. The discovery and understanding of miRNAs has revolutionized the traditional view of gene expression. Alport syndrome （AS） is an inherited disorder of type IV collagen, which most commonly leads to glomerulonephritis and kidney failure. Patients with AS inevitably reach end-stage renal disease and require renal replacement therapy, starting in young adulthood. In this study, Solexa sequencing was used to identify and quantitatively profile small RNAs from an AS family. We identified 30 known miRNAs that showed a sig- nificant change in expression between two individuals. Nineteen miRNAs were up-regulated and eleven were down-regulated. Forty-nine novel miRNAs showed significantly different levels of expression between two individuals. Gene target predictions for the miRNAs revealed that high ranking target genes were implicated in cell, cell part and cellular process categories. The purine metabolism pathway and mitogen-activated protein kinase （MAPK） signaling pathway were enriched by the largest number of target genes. These results strengthen the notion that miRNAs and their target genes are involved in AS and the data advance our understanding of miRNA function in the patho- genesis of AS.

目的:寻找来源于Alport综合征患者与正常对照者的多能干细胞差异性表达的microR NA,并对差异性表达的microR NA靶基因进行预测。创新点:本研究不同于一般的试验标本,试验标本是来源于尿肾脏管细胞诱导而成的多能干细胞。基于Alport综合征是遗传疾病,我们对一遗传家系进行了系统的分析。寻找特异性的差异性表达microR NA及其靶基因,从基因水平对Alport综合征进行研究。方法:在前期工作中,成功地从实验者与对照者的尿肾脏管细胞诱导成多能干细胞。运用高通量测序技术分析并发现实验者与对照者之间差异性表达的microR NA。对差异性表达的microR NA靶基因进行预测,并进行靶基因聚集分析,研究靶基因主要参与的生物学过程。同时进行靶基因信号传导通路的分析,研究靶基因主要参与的细胞信号传导通路。结论:在实验组与对照组之间,发现了30个具有显著差异性表达的microR NAs,包括19个上调表达与11个下调表达。差异性表达的microR NA的靶基因主要聚集在细胞膜和细胞代谢过程;靶基因主要参与嘌呤代谢通路与丝裂原活化蛋白激酶(MAPK)通路。