LncRNA XIST serves as a ceRNA to regulate the expression of ASF1A, BRWD1M, and PFKFB2 in kidney transplant acute kidney injury via sponging hsa-miR-212-3p and hsa-miR-122-5p

Abstract

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].

Keywords: Acute kidney injury; competing endogenous RNAs; differentially expressed microRNAs; kidney transplantation; target genes.

Figure 1.

The heatmap for differentially expressed miRNAs. A: ZERO group; B: POST group. Top color represents grouping, red: disease group, green: control group; blue in the heatmap: down-regulated expression, orange: up-regulated expression.

Figure 2.

The network based on these 13 miRNAs and 100 target genes. Orange circle nodes: target genes; blue triangle: up-regulated miRNAs; Yellow arrow: down-regulated miRNAs.

Figure 3.

The result of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for the miRNAs that the number of target genes≥5. A: GO, lateral axis: miRNAs, numbers in parentheses: the number of genes; vertical axis: the name of GO terms; the size of round dot: GeneRatio, bigger dot represents more miRNAs enriched in this term, smaller p value represents higher significance; B: KEGG, lateral axis: miRNAs, numbers in parentheses: the number of genes; vertical axis: the name of KEGG pathway; the size of round dot: GeneRatio, bigger dot represents more miRNAs enriched in this term, smaller p value represents higher significance.

Figure 4.

Protein–protein interaction (PPI) networks. Orange circle nodes: target genes; yellow triangle: up-regulated miRNAs; blue arrow: down-regulated miRNAs; line without arrow: PPI relations; line with arrow: miRNA-gene regulating relations.

Figure 5.

Competing endogenous RNAs (ceRNA) regulating networks. Orange circle nodes: target genes; green diamond: lncRNA; blue arrow: down-regulated miRNAs; yellow triangle: up-regulated miRNAs.