The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223
Abstract
AIMS: Sustained cardiac hypertrophy accompanied by maladaptive cardiac remodelling represents an early event in the clinical course leading to heart failure. Maladaptive hypertrophy is considered to be a therapeutic target for heart failure. However, the molecular mechanisms that regulate cardiac hypertrophy are largely unknown. METHODS AND RESULTS: Here we show that a circular RNA (circRNA), which we term heart-related circRNA (HRCR), acts as an endogenous miR-223 sponge to inhibit cardiac hypertrophy and heart failure. miR-223 transgenic mice developed cardiac hypertrophy and heart failure, whereas miR-223-deficient mice were protected from hypertrophic stimuli, indicating that miR-223 acts as a positive regulator of cardiac hypertrophy. We identified ARC as a miR-223 downstream target to mediate the function of miR-223 in cardiac hypertrophy. Apoptosis repressor with CARD domain transgenic mice showed reduced hypertrophic responses. Further, we found that a circRNA HRCR functions as an endogenous miR-223 sponge to sequester and inhibit miR-223 activity, which resulted in the increase of ARC expression. Heart-related circRNA directly bound to miR-223 in cytoplasm and enforced expression of HRCR in cardiomyocytes and in mice both exhibited attenuated hypertrophic responses. CONCLUSIONS: These findings disclose a novel regulatory pathway that is composed of HRCR, miR-223, and ARC. Modulation of their levels provides an attractive therapeutic target for the treatment of cardiac hypertrophy and heart failure.
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Cited by
The biogenesis, biology and characterization of circular RNAs
Kristensen, L. S., Andersen, M. S., Stagsted, L. V. W., Ebbesen, K. K., Hansen, T. B., & Kjems, J. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0158-7 · Cited by 4,823
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Metadata
- Authors
- Wang, K., Long, B., Liu, F., Wang, J.-X., Liu, C.-Y., Zhao, B., Zhou, L.-Y., Sun, T., Wang, M., Yu, T., Gong, Y., Liu, J., Dong, Y.-H., Li, N., & Li, P.-F.
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-01-21
- Volume
- 37
- Issue
- 33
- Pages
- 2602-2611
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- OpenAlex
- W2346480860
- Cited by
- 871
- References
- 45
- FWCI
- 45.90
- Type
- journal article
- Language
- en
- Open access
- closed
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- Wang, K., Long, B., Liu, F., Wang, J.-X., Liu, C.-Y., Zhao, B., Zhou, L.-Y., Sun, T., Wang, M., Yu, T., Gong, Y., Liu, J., Dong, Y.-H., Li, N., & Li, P.-F. (2016). A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223. European Heart Journal. https://doi.org/10.1093/eurheartj/ehv713
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