Circular RNA expression alterations and function prediction in OSA-induced pancreatic injury in mice: New insights
Qingshi Chen1, Jiayu Lin1, Zhiyu Chen2
1Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Objectives:
Increasing studies have shown that circular RNAs (circRNAs) participate in the pathogenesis and progression of many diseases. However, the function of circRNAs in obstructive sleep apnea (OSA)-induced pancreatic damage has not been fully elucidated. In this study, the altered circRNA profiles in a chronic intermittent hypoxia (CIH) mouse model were investigated, aiming to provide novel clues for delineating the underlying mechanisms of OSA-induced pancreatic injury.
Methods:
A CIH mouse model was established. circRNA microarray was then applied to profile circRNA expression in pancreatic samples from CIH groups and controls. Our preliminary findings were validated by qRT-PCR. Subsequently, GO and KEGG pathway analyses were carried out to annotate the biological functions of target genes of circRNAs. Lastly, we constructed a circRNA-miRNA-mRNA (ceRNA) network according to the predicted circRNA-miRNA and miRNA-mRNA pairs.
Results:
A total of 26 circRNAs were identified to be differentially expressed, with 5 downregulated and 21 upregulated in the CIH model mice. Six selected circRNAs were preliminarily used to confirm the results by qRT-PCR, which were consistent with microarray. GO and pathway analysis indicated that numerous mRNAs were involved in the MAPK signaling pathway. The ceRNA analysis displayed the broad potentials of the dysregulated circRNAs to modulate their target genes by acting as miRNAs sponges.
Conclusions:
Taken together, our study first revealed the specific expression profile of circRNAs in CIH-induced pancreatic injury, which suggested a novel focus for investigating the molecular mechanism of OSA-induced pancreatic damage through modulating circRNAs.
Insights
This study identified altered circular RNA (circRNA) profiles in mice with chronic intermittent hypoxia (CIH), revealing potential mechanisms for obstructive sleep apnea (OSA)-induced pancreatic damage. These findings highlight circRNAs as key players in OSA-related pancreatic injury.
Area of Science:
- Molecular Biology
- Genomics
- Pathophysiology
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in various disease processes.
- The specific involvement of circRNAs in pancreatic damage induced by obstructive sleep apnea (OSA) remains largely unexplored.
- Chronic intermittent hypoxia (CIH) is a hallmark of OSA and can lead to systemic complications, including organ damage.
Purpose of the Study:
- To investigate the circRNA expression profile in pancreatic tissue under CIH conditions.
- To identify potential circRNAs involved in the pathogenesis of OSA-induced pancreatic injury.
- To explore the underlying molecular mechanisms, including circRNA-miRNA-mRNA interactions.
Main Methods:
- Establishment of a CIH mouse model.
- circRNA microarray analysis of pancreatic tissue.
- Validation of differentially expressed circRNAs using qRT-PCR.
- Gene Ontology (GO) and KEGG pathway analyses.
- Construction of a circRNA-miRNA-mRNA (ceRNA) network.
Main Results:
- Identification of 26 differentially expressed circRNAs (5 downregulated, 21 upregulated) in the CIH model.
- Validation of microarray findings through qRT-PCR.
- Enrichment analysis indicated involvement of the MAPK signaling pathway.
- ceRNA network analysis suggested circRNAs act as miRNA sponges to regulate target genes.
Conclusions:
- This study provides the first comprehensive circRNA expression profile in CIH-induced pancreatic injury.
- Dysregulated circRNAs may play a significant role in the molecular mechanisms of OSA-induced pancreatic damage.
- Targeting circRNAs offers a potential novel therapeutic strategy for OSA-related pancreatic complications.
