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Updated: Dec 1, 2025
Identification of Circular RNAs using RNA Sequencing
Published on: November 14, 2019
Genomic analysis of circular RNAs in heart
Kunzhe Dong1, Xiangqin He1, Huabo Su1,2
1Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, 1459 Laney Walker Blvd, Augusta, GA, 30912, USA.
Insights
Circular RNAs (circRNAs) are key in heart function and disease. This study identifies novel cardiac circRNAs and reveals their dysregulation in dilated cardiomyopathy (DCM), offering new insights into heart failure mechanisms.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Genomics
Background:
- Heart failure is a major cause of death worldwide.
- Circular RNAs (circRNAs) are emerging as critical players in cellular physiology and pathology.
- Understanding circRNA roles in heart disease is crucial for developing new therapies.
Purpose of the Study:
- To identify and characterize cardiac-specific circRNAs.
- To investigate the role of circRNAs in dilated cardiomyopathy (DCM).
- To explore the potential of circRNAs as miRNA sponges in heart disease.
Main Methods:
- De novo analysis of whole transcriptome data from human heart samples (normal and DCM).
- Comparison with existing circRNA datasets from human, mouse, and rat hearts.
- Bioinformatic prediction of miRNA-binding potential for identified circRNAs.
Main Results:
- A comprehensive list of reliably detected cardiac circRNAs was generated.
- Top 30 abundant circRNAs in healthy hearts were identified, including novel ones like circHIPK3_11 and circTULP4_1.
- Significant dysregulation of circRNAs, including novel read-through (rt)-circRNAs, was observed in DCM, particularly from TTN and RYR2 loci.
- Cardiac circRNAs, such as circALMS1_6, show potential for sponging disease-related microRNAs like miR-133.
Conclusions:
- This study provides a valuable resource for circRNA research in human heart disease.
- Novel circRNAs and their dysregulation in DCM offer new avenues for understanding heart failure.
- The findings establish a framework for identifying circRNAs in other tissues and diseases.
Background:
Heart failure is a leading cause of human morbidity and mortality. Circular RNAs (circRNAs) are a newly discovered class of RNA that have been found to have important physiological and pathological roles. In the current study, we de novo analyzed existing whole transcriptome data from 5 normal and 5 dilated cardiomyopathy (DCM) human heart samples and compared the results with circRNAs that have been previously reported in human, mouse and rat hearts.
Results:
Our analysis identifies a list of cardiac circRNAs that are reliably detected in multiple studies. We have also defined the top 30 most abundant circRNAs in healthy human hearts which include some with previously unrecognized cardiac roles such as circHIPK3_11 and circTULP4_1. We further found that many circRNAs are dysregulated in DCM, particularly transcripts originating from DCM-related gene loci, such as TTN and RYR2. In addition, we predict the potential of cardiac circRNAs to sponge miRNAs that have reported roles in heart disease. We found that circALMS1_6 has the highest potential to bind miR-133, a microRNA that can regulate cardiac remodeling. Interestingly, we detected a novel class of circRNAs, referred to as read-though (rt)-circRNAs which are produced from exons of two different neighboring genes. Specifically, rt-circRNAs from SCAF8 and TIAM2 were observed to be dysregulated in DCM and these rt-circRNAs have the potential to sponge multiple heart disease-related miRNAs.
Conclusions:
In summary, this study provides a valuable resource for exploring the function of circRNAs in human heart disease and establishes a functional paradigm for identifying novel circRNAs in other tissues.
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