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Published on: December 28, 2011
Circular RNA Expression Profiles and Bioinformatic Analysis in Mouse Models of Obstructive Sleep Apnea-Induced
Suxian Lai1, Lijun Chen2, Pingyun Zhan3
1Department of Neonatology, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, China.
Abstract:
Circular RNAs (circRNAs) participate in the development of various kinds of diseases. However, the function and roles of circRNAs in obstructive sleep apnea (OSA)-induced cardiovascular disease remain poorly understood. Therefore, we sought to explore the circRNA expression profiles and predict their functions in OSA-induced cardiac injury with the use of bioinformatics analysis. The model of OSA was established in mouse treated by chronic intermittent hypoxia (CIH) exposure. Then, we screened the circRNA profile using circRNA microarray. By comparing circRNA expression in three matched pairs of CIH-treated cardiac tissues and controls, differentially expressed circRNAs were identified in the CIH groups. Comparison of the selected circRNAs expression levels was performed between qRT-PCR and microarray. Meanwhile, we employed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to predict the functions of these selected circRNAs. Finally, we constructed a circRNA-miRNA-mRNA network based on the target prediction. It was found that a total of 124 circRNAs were differentially expressed in CIH-treated cardiac tissues (p ≤ 0.05, fold-change ≥ 1.5). Among them, 23 circRNAs were significantly down-regulated, and the other 101 were up-regulated. Then, ten circRNAs were randomly selected to validate the reliability of the microarray results by using qRT-PCR. Next, we conducted the GO and KEGG pathway analysis to explore the parental genes functions of differentially expressed circRNA. Finally, two significantly differentially expressed circRNAs (mmu_circRNA_014309 and mmu_circRNA_21856) were further selected to create a circRNA-miRNA-mRNA regulation network. Our study did first reveal that the differentially expressed circRNAs played a vital role in the pathogenesis of OSA-induced cardiac damage. Thus, our findings bring us closer to unraveling the pathophysiologic mechanisms and eliciting novel therapeutic targets for the treatment of OSA-associated cardiovascular diseases.
Insights
This study identifies differentially expressed circular RNAs (circRNAs) in mice with obstructive sleep apnea (OSA), revealing their crucial role in cardiac damage and offering potential therapeutic targets for OSA-related cardiovascular diseases.
Area of Science:
- Molecular Biology
- Genomics
- Cardiovascular Research
Background:
- Circular RNAs (circRNAs) are implicated in various diseases, but their function in obstructive sleep apnea (OSA)-induced cardiovascular disease is unclear.
- Understanding circRNA roles is critical for developing targeted therapies for OSA-related cardiac complications.
Purpose of the Study:
- To explore circRNA expression profiles in OSA-induced cardiac injury using bioinformatics.
- To predict the functions of differentially expressed circRNAs and construct regulatory networks.
Main Methods:
- Established a mouse model of OSA via chronic intermittent hypoxia (CIH) exposure.
- Screened circRNA profiles using circRNA microarray and validated with qRT-PCR.
- Utilized Gene Ontology (GO) and KEGG pathway analyses for functional prediction.
- Constructed circRNA-miRNA-mRNA networks for identified circRNAs.
Main Results:
- Identified 124 differentially expressed circRNAs in CIH-treated cardiac tissues (101 up-regulated, 23 down-regulated).
- Validated microarray results using qRT-PCR for ten selected circRNAs.
- GO and KEGG analyses predicted functions of parental genes of differentially expressed circRNAs.
- Constructed a circRNA-miRNA-mRNA network involving mmu_circRNA_014309 and mmu_circRNA_21856.
Conclusions:
- This study is the first to reveal the significant role of differentially expressed circRNAs in the pathogenesis of OSA-induced cardiac damage.
- Findings advance the understanding of pathophysiological mechanisms of OSA-associated cardiovascular diseases.
- Identified circRNAs represent potential novel therapeutic targets for OSA-related cardiovascular conditions.
