LAUSR

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.