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Published on: October 26, 2020
CircRNA expression profiles and functional analysis in a mouse model of chronic intermittent hypoxia-induced renal
Qingshi Chen1, Zhenzhen Hong1, Zhiyu Chen2
1Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Abstract:
Increasing evidence has demonstrated that circular RNAs (circRNAs) play crucial roles in the pathogenesis of multiple diseases. However, the functions of circRNAs in renal injury induced by obstructive sleep apnea (OSA) are poorly understood. The aim of this current study is to identify the global changes of circRNAs expression in OSA-induced renal damage. The mouse model of OSA treated by chronic intermittent hypoxia (CIH) was established. We assessed the expression profiles of circRNAs in CIH caused renal injury by microarray analysis. Bioinformatic analyses were further performed by us to assess those differentially expressed circRNAs. Quantitative realtime PCR (qRT-PCR) were then conducted to assure the data of microarray. Finally, a circRNA-miRNA -mRNA competing endogenous RNA (ceRNA) regulatory network was constructed. We found 11 upregulated and 13 downregulated circRNAs in CIH-induced renal injury. The qRT-PCR validated that the six selected circRNAs were identical to the results of microarray. Both Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were further employed to annotate the potential functions of dysregulated circRNAs. Finally, we established a ceRNA network to predict the target genes of circRNAs. In general, our results first illustrate that circRNAs are aberrantly expressed in OSA-induced renal injury, which might aid in offering novel genetic insights into this disease and potential therapeutic targets for OSA-associated chronic kidney disease.
Insights
Circular RNAs (circRNAs) are altered in obstructive sleep apnea (OSA)-induced kidney damage. This study identifies specific circRNAs and pathways involved, offering potential therapeutic targets for OSA-related chronic kidney disease.
Area of Science:
- Molecular Biology
- Genomics
- Renal Pathophysiology
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in disease pathogenesis.
- The specific involvement of circRNAs in renal injury associated with obstructive sleep apnea (OSA) remains largely unexplored.
Purpose of the Study:
- To comprehensively identify global circRNA expression changes in a mouse model of OSA-induced renal damage.
- To elucidate the potential functions and regulatory networks of dysregulated circRNAs in this condition.
Main Methods:
- Establishment of a mouse model for OSA using chronic intermittent hypoxia (CIH).
- Microarray analysis to assess circRNA expression profiles in renal tissues.
- Bioinformatic analysis, quantitative real-time PCR (qRT-PCR), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.
- Construction of a circRNA-miRNA-mRNA competing endogenous RNA (ceRNA) regulatory network.
Main Results:
- Identified 11 upregulated and 13 downregulated circRNAs in CIH-induced renal injury.
- QRT-PCR validation confirmed the microarray findings for selected circRNAs.
- GO and KEGG analyses provided insights into the potential functions of dysregulated circRNAs.
- A circRNA-mediated ceRNA network was constructed to predict target gene interactions.
Conclusions:
- CircRNAs are significantly and aberrantly expressed in OSA-induced renal injury.
- These findings provide novel genetic insights into OSA-associated kidney disease.
- Identified circRNAs represent potential therapeutic targets for OSA-related chronic kidney disease.
