Nephrology Department, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
Cardiology Department, Dalian Central Hospital, Dalian, Liaoning, China.
Cell Cycle. 2020 Feb;19(3):290-299. doi: 10.1080/15384101.2019.1707454. Epub 2020 Jan 8.
We aimed to identify potential mechanism associated with acute kidney injury (AKI) after kidney transplantation. The dataset GSE53771, which contained 18 zero-hour (ZERO group) and 18 selected post-transplant (POST group) biopsy samples from 18 kidney allografts (8 AKI and 10 controls) was downloaded from GEO database. Differentially expressed miRNAs (DEMIs) were screened using limma package, and bidirectional hierarchical clustering of the DEMIs was performed using the pheatmap package. Target genes of DEMIs were predicted by miRWalk 2.0, miRNA-target genes networks were presented using Cytoscape, protein-protein interaction (PPI) networks were constructed by STRING (version:10.0) database, and competing endogenous RNAs (ceRNA) regulating network were constructed using Cytoscape. In ZERO and POST groups, a total of 4 and 24 differentially expressed miRNAs were obtained in AKI samples compared with control, respectively. Specifically, 71 lncRNAs were obtained to interact with five miRNAs (hsa-miR-215-5p, hsa-miR-192-5p, hsa-miR-422a, hsa-miR-212-3p and hsa-miR-122-5p). Histone chaperone ASF1A (ASF1A) and bromodomain and WD repeat-containing protein 1(BRWD1) were targeted by hsa-miR-212-3p in PPI network. In ceRNA network, lncRNA XIST could interact with four miRNAs (hsa-miR-212-3p, hsa-miR-122-5p, hsa-miR-215-5p, and hsa-miR-192-5p). LncRNA XIST might serve as a ceRNA to sponge hsa-miR-212-3p to regulate the development of AKI via altering the expression of ASF1A/BRWD1. Furthermore, lncRNA XIST could also interact with hsa-miR-122-5p to modulate the expression of PFKFB2 in thyroid hormone signaling pathway and AMPK signaling pathway. LncRNA XIST can serve as a ceRNA to sponge hsa-miR-212-3p and hsa-miR-122-5p to regulate AKI progression via modulating the expression of ASF1A, BRWD1, and PFKFB2.[Figure: see text].
我们旨在确定与肾移植后急性肾损伤(AKI)相关的潜在机制。从 GEO 数据库下载了数据集 GSE53771,其中包含 18 个零时间点(ZERO 组)和 18 个选定的移植后(POST 组)活检样本,来自 18 个肾移植(8 个 AKI 和 10 个对照)。使用 limma 包筛选差异表达的 miRNAs(DEMIs),使用 pheatmap 包对 DEMIs 进行双向层次聚类。使用 miRWalk 2.0 预测 DEMIs 的靶基因,使用 Cytoscape 展示 miRNA-靶基因网络,使用 STRING(版本:10.0)数据库构建蛋白质-蛋白质相互作用(PPI)网络,使用 Cytoscape 构建竞争内源性 RNA(ceRNA)调节网络。在 ZERO 和 POST 组中,与对照组相比,AKI 样本中分别获得了 4 个和 24 个差异表达的 miRNAs。具体而言,获得了 71 个 lncRNA 与五个 miRNAs(hsa-miR-215-5p、hsa-miR-192-5p、hsa-miR-422a、hsa-miR-212-3p 和 hsa-miR-122-5p)相互作用。组蛋白伴侣 ASF1A(ASF1A)和溴结构域和 WD 重复蛋白 1(BRWD1)是 PPI 网络中 hsa-miR-212-3p 的靶标。在 ceRNA 网络中,lncRNA XIST 可以与四个 miRNAs(hsa-miR-212-3p、hsa-miR-122-5p、hsa-miR-215-5p 和 hsa-miR-192-5p)相互作用。lncRNA XIST 可能作为 ceRNA 通过改变 ASF1A/BRWD1 的表达来海绵吸附 hsa-miR-212-3p,从而调节 AKI 的发展。此外,lncRNA XIST 还可以与 hsa-miR-122-5p 相互作用,调节甲状腺激素信号通路和 AMPK 信号通路中 PFKFB2 的表达。lncRNA XIST 可以作为 ceRNA 通过调节 ASF1A、BRWD1 和 PFKFB2 的表达来海绵吸附 hsa-miR-212-3p 和 hsa-miR-122-5p,从而调节 AKI 的进展。[图:见正文]。