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Circular RNA mediated gene regulation in chronic diabetic complications
Nikhil S Patil1, Biao Feng2, Zhaoliang Su3
1Michael G Degroote School of Medicine, McMaster University, Hamilton, ON, Canada.
Abstract:
Chronic diabetic complications affect multiple organs causing widespread organ damage. Although there are some commonalities, the phenotype of such changes show tissue specific variation. Given this, we examined whether differences in circular RNA (circRNA) mediated gene regulatory mechanisms contribute to changes in gene expression at the basal level and in diabetes. CircRNAs are single-stranded RNA with covalently closed loop structures and act as miRNA sponges, factors of RNA splicing, scaffolding for proteins, regulators of transcription, and modulators of the expression of parental genes, among other roles. We examined heart and retinal tissue from Streptozotocin-induced diabetic mice with established diabetes related tissue damage and tissue from non-diabetic controls. A custom array analysis was performed and the data were analysed. Two major circRNA mediated processes were uniquely upregulated in diabetic heart tissue, namely, positive regulation of endothelial cell migration and regulation of mitochondria: mitochondrial electron transport. In the retina, circRNAs regulating extracellular matrix protein production and endothelial to mesenchymal transition (EndMT) were found to be upregulated. The current study identified regulatory and potential pathogenetic roles of specific circRNA in diabetic retinopathy and cardiomyopathy. Understanding such novel mechanisms, may in the future, be useful to develop RNA based treatment strategies.
Insights
This study reveals distinct circular RNA (circRNA) roles in diabetic heart and retinal damage. Understanding these circRNA mechanisms may lead to new RNA-based treatments for diabetic complications.
Area of Science:
- Molecular Biology
- Genetics
- Cardiology
- Ophthalmology
Background:
- Chronic diabetic complications cause significant, multi-organ damage with tissue-specific variations.
- Circular RNAs (circRNAs) are versatile molecules involved in gene regulation, including miRNA sponging, transcriptional regulation, and protein scaffolding.
- Tissue-specific differences in gene regulation may underlie varied diabetic complications.
Purpose of the Study:
- To investigate if distinct circular RNA (circRNA)-mediated gene regulatory mechanisms contribute to gene expression changes in diabetic heart and retinal tissues.
- To identify specific circRNAs involved in the pathogenesis of diabetic cardiomyopathy and retinopathy.
Main Methods:
- Analysis of heart and retinal tissues from Streptozotocin-induced diabetic mice and non-diabetic controls.
- Custom array analysis to identify differentially expressed circRNAs.
- Data analysis to pinpoint circRNA-mediated regulatory processes.
Main Results:
- Diabetic heart tissue showed upregulated circRNA activity in endothelial cell migration and mitochondrial electron transport.
- Diabetic retinal tissue exhibited upregulated circRNAs involved in extracellular matrix production and endothelial-to-mesenchymal transition (EndMT).
Conclusions:
- Specific circRNAs play unique regulatory and potentially pathogenetic roles in diabetic cardiomyopathy and retinopathy.
- Elucidating these novel circRNA mechanisms could pave the way for future RNA-based therapeutic strategies for diabetic complications.
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