Xin Guangda, Chen Rui, Zhang Xiaofei
Department of Nephrology, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
Department of Pediatrics, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
Gene. 2018 Apr 15;650:77-85. doi: 10.1016/j.gene.2018.01.063. Epub 2018 Feb 2.
The present study aimed to investigate the molecular mechanism underlying congenital obstructive nephropathy (CON).
The microarray dataset GSE70879 was downloaded from the Gene Expression Omnibus, including 3 kidney samples of megabladder mice and 4 control kidneys. Using this dataset, differentially expressed miRNAs (DEMs) were identified between the kidney samples from megabladder mice and controls, followed by identification of the target genes for these DEMs and construction of a DEM and target gene interaction network. Additionally, the target genes were subjected to Gene Ontology and pathway enrichment analyses, and were used for construction of a protein-protein interaction (PPI) network. Finally, regulatory networks were constructed to analyze transcription factors for the key miRNAs.
From 17 DEMs identified between kidney samples of megabladder mice and controls, 3 key miRNAs were screened, including mmu-miR-150-5p, mmu-miR-374b-5p and mmu-miR-126a-5p. The regulatory networks identified vascular endothelial growth factor A (Vegfa) as the common target gene of mmu-miR-150-5p and five transcription factors, including nuclear receptor subfamily 4, group A, member 2 (Nr4a2), Jun dimerisation protein 2 (Jdp2), Kruppel-like factor 6 (Klf6), Neurexophilin-3 (Nxph3) and RNA binding motif protein 17 (Rbm17). The gene encoding phosphatase and tensin homolog (Pten) was found to be co-regulated by mmu-miR-374b-5p and high mobility group protein A1 (Hmga1), whereas the kirsten rat sarcoma viral oncogene (Kras) was identified as a common target gene of mmu-miR-126a-5p and paired box 6 (Pax6).
In summary, the above-listed key miRNAs, transcription factors and key genes may be involved in the development of CON.
本研究旨在探究先天性梗阻性肾病（CON）的分子机制。
从基因表达综合数据库下载微阵列数据集GSE70879，其中包括3个巨膀胱小鼠的肾脏样本和4个对照肾脏样本。利用该数据集，鉴定巨膀胱小鼠肾脏样本与对照样本之间差异表达的miRNA（DEM），随后鉴定这些DEM的靶基因并构建DEM与靶基因的相互作用网络。此外，对靶基因进行基因本体论和通路富集分析，并用于构建蛋白质-蛋白质相互作用（PPI）网络。最后，构建调控网络以分析关键miRNA的转录因子。
在巨膀胱小鼠肾脏样本与对照样本之间鉴定出的17个DEM中，筛选出3个关键miRNA，包括mmu-miR-150-5p、mmu-miR-374b-5p和mmu-miR-126a-5p。调控网络确定血管内皮生长因子A（Vegfa）是mmu-miR-150-5p和5个转录因子的共同靶基因，这5个转录因子包括核受体亚家族4 A组成员2（Nr4a2）、Jun二聚化蛋白2（Jdp2）、 Kruppel样因子6（Klf6）、神经亲环蛋白3（Nxph3）和RNA结合基序蛋白17（Rbm17）。发现编码磷酸酶和张力蛋白同源物（Pten）的基因受mmu-miR-374b-5p和高迁移率族蛋白A1（Hmga1）共同调控，而 Kirsten大鼠肉瘤病毒癌基因（Kras）被确定为mmu-miR-126a-5p和配对盒6（Pax6）的共同靶基因。
综上所述，上述关键miRNA、转录因子和关键基因可能参与了CON的发生发展。
