Identification of lncRNA-miRNA-mRNA ceRNA network as biomarkers for acute kidney injury
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Updated: Jul 12, 2025
A Quantitative Detection Method for MicroRNAs in the Kidney of an Ischemic Kidney Injury Mouse Model
Published on: September 11, 2020
1Department of Nephrology, Liuzhou People's Hospital Liuzhou, Guangxi, China.
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.
Insights
This study identified novel long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) involved in acute kidney injury (AKI) induced by ischemia/reperfusion or cisplatin. These findings offer potential biomarkers for AKI diagnosis and therapeutic targets.
Area of Science:
- Molecular Biology
- Genomics
- Biochemistry
Background:
- Acute kidney injury (AKI) presents a significant global health challenge due to high morbidity and mortality rates.
- Understanding the molecular underpinnings of AKI is crucial for developing effective diagnostic and therapeutic strategies.
Purpose of the Study:
- To identify key RNA molecules, including long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs), implicated in acute kidney injury (AKI) induced by ischemia/reperfusion (I/R) or cisplatin (CIS).
- To construct a competing endogenous RNA (ceRNA) regulatory network for AKI and analyze associated biological processes and signaling pathways.
Main Methods:
- Downloaded and analyzed microarray datasets (GSE106993, GSE130814, GSE98622) from the Gene Expression Omnibus database.
- Identified differentially expressed lncRNAs (DE-lncRNAs) and DE-mRNAs, predicted miRNA targets, and constructed ceRNA networks.
- Performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and constructed protein-protein interaction (PPI) networks.
- Utilized CIBERSORT to analyze immune cell infiltration patterns in AKI.
Main Results:
- Identified 2 DE-lncRNAs and 375 DE-mRNAs in I/R and CIS-induced AKI.
- Constructed a common ceRNA network involving 2 lncRNAs (Platr7, Gm15611), 65 miRNAs, and 167 mRNAs.
- The 167 common mRNAs were significantly enriched in transcription regulation, metabolic processes, cell proliferation, extracellular region, DNA binding, and the MAPK and JAK-STAT signaling pathways.
- Mitochondrial apoptosis-related genes Pmaip1 and Nptx1 showed high expression; significant differences in immune cell infiltration were observed between AKI and normal groups.
Conclusions:
- Novel lncRNAs and mRNAs were identified as potential biomarkers for AKI diagnosis and therapeutic targets.
- The constructed ceRNA network provides valuable insights into the molecular mechanisms underlying AKI onset and progression.
- Further exploration of these identified RNAs and networks can advance AKI research and clinical management.
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