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Updated: Jan 21, 2026

Identification of Circular RNAs using RNA Sequencing
Published on: November 14, 2019
A Novel Circular RNA Mediates Pyroptosis of Diabetic Cardiomyopathy by Functioning as a Competing Endogenous RNA
Fan Yang1, Anqi Li2, Ying Qin3
1Department of Endocrinology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Insights
Diabetic cardiomyopathy involves programmed cell death and inflammation. This study identifies a circular RNA (circRNA), CACR, that exacerbates this condition by regulating the miR-214-3p/caspase-1 pathway, suggesting CACR as a potential therapeutic target.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- RNA Biology
Background:
- Diabetic cardiomyopathy (DCM) is a significant cause of mortality in diabetic patients, characterized by cardiomyocyte death and inflammation.
- Circular RNAs (circRNAs) are emerging as key regulators in disease, but their specific role in DCM requires further investigation.
- Previous research indicated pyroptosis activation in high-glucose conditions and identified miR-214-3p's regulation of caspase-1.
Purpose of the Study:
- To investigate the involvement of circRNA in DCM-related pyroptosis.
- To elucidate the potential mechanism involving the miR-214-3p/caspase-1 pathway.
Main Methods:
- Identification and naming of a specific circRNA, hsa_circ_0076631, as caspase-1-associated circRNA (CACR).
- Assessment of CACR levels in high-glucose-treated cardiomyocytes and serum from diabetic patients.
- Experimental manipulation of CACR and miR-214-3p levels in cardiomyocytes to evaluate effects on pyroptosis and caspase-1 activation.
Main Results:
- CACR levels were elevated in high-glucose-treated cardiomyocytes and diabetic patient serum.
- CACR was found to sponge miR-214-3p, inhibiting its expression.
- Knockdown of CACR mitigated high-glucose-induced caspase-1 activation and pyroptosis.
- Silencing miR-214-3p partially reversed the protective effects of CACR knockdown.
Conclusions:
- CACR plays a role in DCM-related pyroptosis via the CACR/miR-214-3p/caspase-1 pathway.
- CACR represents a potential novel therapeutic target for managing diabetic cardiomyopathy.
Abstract:
Diabetic cardiomyopathy (DCM) is a vital cause of fatalities in diabetic patients. The programmed death of cardiomyocytes and inflammation critically contribute to cardiac hypertrophy and fibrosis in DCM. Furthermore, circular RNA (circRNA) is a key regulator of various diseases. However, the role of circRNAs in DCM remains to be elucidated. Our previous study found that pyroptosis was markedly activated in the cardiomyocytes subjected to high-glucose conditions, and miR-214-3p regulated the expression of caspase-1. The aim of this study was to elucidate whether circRNA is involved in DCM pyroptosis via the miR-214-3p/caspase-1 pathway. Herein, we identified that hsa_circ_0076631, named caspase-1-associated circRNA (CACR), was increased both in high-glucose-treated cardiomyocytes and in the serum of diabetic patients. CACR also sponged an endogenous miR-214-3p to sequester and inhibit its expression. CACR knockdown in cardiomyocytes counteracted high-glucose-induced caspase-1 activation. Conversely, miR-214-3p knockdown partially abolished the beneficial effects of CACR silencing on pyroptosis in cardiomyocytes. Therefore, this study elucidated that CACR might be a novel therapeutic target via the CACR/miR-214-3p/caspase-1 pathway in DCM.
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