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CircNCX1: the "Lord of the Ring" in the Heart - Insight into Its Sequence Characteristic, Expression, Molecular
Lin Ding1, Mengyang Li1, Fuqing Yang1
1School of Basic Medical Sciences, Qingdao University, Qingdao, 266071, China.
Abstract:
Circular RNAs (circRNAs) are covalently closed single-stranded RNAs with regulatory activity and regarded as new types of therapeutic targets in diseases such as cancers. By means of RNA-Seq technology, numerous cardiac circRNAs were discovered. Although some candidates were detected to involve in heart disease in murine model, relative low sequence conservation and expression level of their human homologs might result in an insignificant, even distinct effect in the human heart. Therefore, the therapeutic significance of circRNAs should be more strictly considered. It is also necessary to discuss which circRNA is suitable for being applied in heart disease treatment. Here, we are willing to introduce a ~ 1830 nt circular transcript generated from single exon of sodium/calcium exchanger 1 (ncx1) gene (also called solute carrier family 8 member A1, slc8a1), usually named circNCX1 or circSLC8A1, which is gradually coming into our view. circNCX1 is one of the most cardiac-enriched circRNAs. It is widely existent in vertebrate and relatively conserved, indicating its indispensability during the evolution of species. Indeed, circNCX1 was shown to involve in heart development by some expression analysis. It was further revealed that the dysregulation of circNCX1 is one of the key pathogeneses of heart diseases including ischemic cardiac injury and hypertrophic cardiomyopathy. To make the significance of circNCX1 in the heart clear, we comprehensively dissected circNCX1 in the aspects of its parental gene structure, conservation, biogenesis and expression profiles, function, molecular mechanisms, and clinical application in this review. New medicine or therapeutic schedules based on circNCX1 are expected in the future.
Insights
Circular RNAs (circRNAs) are promising therapeutic targets for heart disease. circNCX1, a cardiac-specific circRNA, is conserved across species and plays a key role in heart development and disease pathogenesis.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- RNA Therapeutics
Background:
- Circular RNAs (circRNAs) are emerging as critical regulators with therapeutic potential in various diseases, including cancer.
- While numerous cardiac circRNAs have been identified using RNA-Seq, their conservation and expression in humans require careful consideration for therapeutic applications.
- circNCX1, derived from the sodium/calcium exchanger 1 (ncx1) gene, is a highly cardiac-enriched and conserved circRNA.
Purpose of the Study:
- To comprehensively review the significance of circNCX1 in cardiac function and disease.
- To dissect the structure, biogenesis, expression, function, and molecular mechanisms of circNCX1.
- To explore the potential clinical applications of circNCX1 in treating heart diseases.
Main Methods:
- Literature review and analysis of existing data on circNCX1.
- Examination of parental gene structure, sequence conservation, and expression profiles.
- Investigation of circNCX1's role in cardiac development and disease pathogenesis.
Main Results:
- circNCX1 is highly conserved across vertebrates, suggesting evolutionary importance.
- Dysregulation of circNCX1 is implicated in the pathogenesis of heart diseases like ischemic cardiac injury and hypertrophic cardiomyopathy.
- circNCX1 exhibits significant roles in heart development and function.
Conclusions:
- circNCX1 is a critical cardiac circRNA with conserved functions and therapeutic potential.
- Further research into circNCX1 mechanisms and applications could lead to novel heart disease treatments.
- circNCX1 represents a promising target for future cardiovascular therapies.
