Identification of lncRNA-miRNA-mRNA ceRNA network as biomarkers for acute kidney injury.

Objective: Acute kidney injury (AKI) is a global problem due to its high morbidity and mortality. The aim of this study was to identify the key RNAs involved in the ischemia/reperfusion (I/R) or cisplatin (CIS) induced AKI.

Methods: Gene Expression Omnibus database was used to download the microarray dataset GSE106993, GSE130814 and GSE98622. Differentially expressed lncRNAs (DE-lncRNAs) and DE-mRNAs were identified in I/R and CIS induced AKI. The target miRNAs of DE lncRNAs were predicted from miRDB, and the miRNA of lncRNA target mRNAs were predicted form StarBase dataset. The ceRNA regulatory networks, GO and KEGG enrichment analysis, and protein-protein interaction (PPI) of I/R and CIS induced AKI specific genes were constructed. The CIBESORT was applied to infer the proportion of 22 immune infiltration cells based on gene expression profiles of I/R and CIS induced AKI.

Results: Totally, 2 DE-lncRNAs and 375 DE-mRNAs were identified in I/R and CIS induced AKI. The common ceRNA network was constructed between CIS group and I/R induced AKI group, which contained 2 lncRNAs (Platr7 and Gm15611), 65 mmu-miRNAs and 167 mRNAs. The 167 common mRNAs were enriched in the biological process of transcription regulation, metabolic process, cell proliferation, the cellular component (CC) of extracellular region and space, the molecular function of DNA binding, and transcription regulator activity in CIS and IRI induced AKI. The common 167 mRNAs involved in the MAPK signaling pathway and JAK-STAT signaling pathway were identified. Protein-Protein Interaction (PPI) Network of ceRNAs network expressed gene was constructed, including 81 nodes, which contained 3 upregulated genes and 78 downregulated genes. Among them, mitochondrial apoptosis-related genes Pmaip1 and Nptx1 showed significantly high expression in the GSE98622 and GSE106993 data sets. The investigation to the connection between the gene expression profiles and immune cell infiltration showed considerable differences in immune cell percentage between AKI group and normal group.

Conclusion: Novel lncRNAs and mRNAs were identified, which may serve as potential biomarkers to predict the diagnostic and therapeutic targets for AKI patients based on a large-scale sample. More importantly, the ceRNA network of I/R or CIS induced AKI was constructed, which provides valuable information to further explore the molecular mechanism underlying onset and progression of AKI.