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Identification of circRNAs expression profiles and functional networks in parotid gland of type 2 diabetes mouse
Yan Huang1,2, Hui-Min Liu3, Qian-Ying Mao1
1Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials, 100081, Beijing, P.R. China.
Background:
Circular RNAs (circRNAs) are a novel kind of non-coding RNAs proved to play crucial roles in the development of multiple diabetic complications. However, their expression and function in diabetes mellitus (DM)-impaired salivary glands are unknown.
Results:
By using microarray technology, 663 upregulated and 999 downregulated circRNAs companied with 813 upregulated and 525 downregulated mRNAs were identified in the parotid glands (PGs) of type2 DM mice under a 2-fold change and P < 0.05 cutoff criteria. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis of upregulated mRNAs showed enrichments in immune system process and peroxisome proliferator-activated receptor (PPAR) signaling pathway. Infiltration of inflammatory cells and increased inflammatory cytokines were observed in diabetic PGs. Seven differently expressed circRNAs validated by qRT-PCR were selected for coding-non-coding gene co-expression (CNC) and competing endogenous RNA (ceRNA) networks analysis. PPAR signaling pathway was primarily enriched through analysis of circRNA-mRNA networks. Moreover, the circRNA-miRNA-mRNA networks highlighted an enrichment in the regulation of actin cytoskeleton.
Conclusion:
The inflammatory response is elevated in diabetic PGs. The selected seven distinct circRNAs may attribute to the injury of diabetic PG by modulating inflammatory response through PPAR signaling pathway and actin cytoskeleton in diabetic PGs.
Insights
Circular RNAs (circRNAs) are implicated in diabetic complications. This study reveals elevated inflammation and specific circRNAs in diabetic salivary glands, potentially impacting injury via PPAR signaling and actin cytoskeleton pathways.
Area of Science:
- Molecular Biology
- Genomics
- Endocrinology
Background:
- Circular RNAs (circRNAs) are recognized for their role in diabetic complications.
- Their involvement in diabetes mellitus (DM)-induced salivary gland dysfunction remains unexplored.
Purpose of the Study:
- To investigate the expression and function of circRNAs in the parotid glands of type 2 diabetic mice.
- To elucidate the molecular mechanisms underlying salivary gland impairment in diabetes.
Main Methods:
- Microarray analysis to identify differentially expressed circRNAs and mRNAs in diabetic parotid glands.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.
- Quantitative real-time PCR (qRT-PCR) for validation.
- Construction of coding-non-coding gene co-expression (CNC) and competing endogenous RNA (ceRNA) networks.
Main Results:
- Identified 663 upregulated and 999 downregulated circRNAs, and 813 upregulated and 525 downregulated mRNAs.
- Upregulated mRNAs were enriched in immune system processes and the peroxisome proliferator-activated receptor (PPAR) signaling pathway.
- Observed inflammatory cell infiltration and increased inflammatory cytokines in diabetic parotid glands.
- circRNA-mRNA and circRNA-miRNA-mRNA network analyses highlighted the PPAR signaling pathway and regulation of the actin cytoskeleton.
Conclusions:
- Diabetic parotid glands exhibit an elevated inflammatory response.
- Seven specific circRNAs are identified as potential contributors to diabetic parotid gland injury.
- These circRNAs may modulate the inflammatory response and affect the actin cytoskeleton via the PPAR signaling pathway.
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