Circular Noncoding RNAs As Potential Therapies and Circulating Biomarkers for Cardiovascular Diseases

Overview

Journal Acta Pharmacol Sin

Specialty Pharmacology

Date 2018 Mar 23

PMID 29565037

Citations 52

Authors

Ahmed S Bayoumi

Tatsuya Aonuma

Jian-Peng Teoh

Yao-Liang Tang

Il-Man Kim

Affiliations

Soon will be listed here.

Abstract

Recent advancements in genome-wide analyses and RNA-sequencing technologies led to the discovery of small noncoding RNAs, such as microRNAs (miRs), as well as both linear long noncoding RNAs (lncRNAs) and circular long noncoding RNAs (circRNAs). The importance of miRs and lncRNAs in the treatment, prognosis and diagnosis of cardiovascular diseases (CVDs) has been extensively reported. We also previously reviewed their implications in therapies and as biomarkers for CVDs. More recently, circRNAs have also emerged as important regulators in CVDs. CircRNAs are circular genome products that are generated by back splicing of specific regions of pre-messenger RNAs (pre-mRNAs). Growing interest in circRNAs led to the discovery of a wide array of their pathophysiological functions. CircRNAs have been shown to be key regulators of CVDs such as myocardial infarction, atherosclerosis, cardiomyopathy and cardiac fibrosis. Accordingly, circRNAs have been recently proposed as potential therapeutic targets and biomarkers for CVDs. In this review, we summarize the current state of the literature on circRNAs, starting with their biogenesis and global mechanisms of actions. We then provide a synopsis of their involvement in various CVDs. Lastly, we emphasize the great potential of circRNAs as biomarkers for the early detection of CVDs, and discuss several patents and recent papers that highlight the utilization of circRNAs as promising biomarkers.

Citing Articles

Toward the use of nanopore RNA sequencing technologies in the clinic: challenges and opportunities.

Katopodi X, Begik O, Novoa E Nucleic Acids Res. 2025; 53(5).

PMID: 40057374 PMC: 11890063. DOI: 10.1093/nar/gkaf128.

The synergistic role of gut microbiota and RNA in metabolic diseases: mechanisms and therapeutic insights.

Huang Z, Yao Q, Ma S, Zhou J, Wang X, Meng Q Front Microbiol. 2025; 16:1504395.

PMID: 39944642 PMC: 11814227. DOI: 10.3389/fmicb.2025.1504395.

CircRNA-mediated regulation of cardiovascular disease.

Cheng K, Wang S, Lan T, Mao Z, Xu Y, Shen Q Front Cardiovasc Med. 2024; 11:1411621.

PMID: 39660120 PMC: 11628502. DOI: 10.3389/fcvm.2024.1411621.

Elevated circulating LncRNA NORAD fosters endothelial cell growth and averts ferroptosis by modulating the miR-106a/CCND1 axis in CAD patients.

He T, Pu J, Ge H, Liu T, Lv X, Zhang Y Sci Rep. 2024; 14(1):24223.

PMID: 39414920 PMC: 11484692. DOI: 10.1038/s41598-024-76243-x.

Therapeutic Potential of Natural Compounds Acting through Epigenetic Mechanisms in Cardiovascular Diseases: Current Findings and Future Directions.

Bontempo P, Capasso L, De Masi L, Nebbioso A, Rigano D Nutrients. 2024; 16(15).

PMID: 39125279 PMC: 11314203. DOI: 10.3390/nu16152399.

References

Steinberg B, Mulpuru S, Fang J, Gersh B . Sudden death mechanisms in nonischemic cardiomyopathies: Insights gleaned from clinical implantable cardioverter-defibrillator trials. Heart Rhythm. 2017; 14(12):1839-1848. DOI: 10.1016/j.hrthm.2017.09.025. View

Li M, Ding W, Sun T, Tariq M, Xu T, Li P . Biogenesis of circular RNAs and their roles in cardiovascular development and pathology. FEBS J. 2017; 285(2):220-232. DOI: 10.1111/febs.14191. View

Zhang Y, Zhang X, Chen T, Xiang J, Yin Q, Xing Y . Circular intronic long noncoding RNAs. Mol Cell. 2013; 51(6):792-806. DOI: 10.1016/j.molcel.2013.08.017. View

Park K, Teoh J, Wang Y, Broskova Z, Bayoumi A, Tang Y . Carvedilol-responsive microRNAs, miR-199a-3p and -214 protect cardiomyocytes from simulated ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2016; 311(2):H371-83. PMC: 5005281. DOI: 10.1152/ajpheart.00807.2015. View

Li J, Liu S, Zhou H, Qu L, Yang J . starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 2013; 42(Database issue):D92-7. PMC: 3964941. DOI: 10.1093/nar/gkt1248. View

Holdt L, Stahringer A, Sass K, Pichler G, Kulak N, Wilfert W . Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans. Nat Commun. 2016; 7:12429. PMC: 4992165. DOI: 10.1038/ncomms12429. View

Wang K, Long B, Liu F, Wang J, Liu C, Zhao B . A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223. Eur Heart J. 2016; 37(33):2602-11. DOI: 10.1093/eurheartj/ehv713. View

Gao J, Xu W, Wang J, Wang K, Li P . The Role and Molecular Mechanism of Non-Coding RNAs in Pathological Cardiac Remodeling. Int J Mol Sci. 2017; 18(3). PMC: 5372624. DOI: 10.3390/ijms18030608. View

Liu J, Liu T, Wang X, He A . Circles reshaping the RNA world: from waste to treasure. Mol Cancer. 2017; 16(1):58. PMC: 5345220. DOI: 10.1186/s12943-017-0630-y. View

10.

Zhou B, Yu J . A novel identified circular RNA, circRNA_010567, promotes myocardial fibrosis via suppressing miR-141 by targeting TGF-β1. Biochem Biophys Res Commun. 2017; 487(4):769-775. DOI: 10.1016/j.bbrc.2017.04.044. View

11.

Iparraguirre L, Munoz-Culla M, Prada-Luengo I, Castillo-Trivino T, Olascoaga J, Otaegui D . Circular RNA profiling reveals that circular RNAs from ANXA2 can be used as new biomarkers for multiple sclerosis. Hum Mol Genet. 2017; 26(18):3564-3572. DOI: 10.1093/hmg/ddx243. View

12.

Li Y, Zheng Q, Bao C, Li S, Guo W, Zhao J . Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res. 2015; 25(8):981-4. PMC: 4528056. DOI: 10.1038/cr.2015.82. View

13.

Bazan H, Hatfield S, Brug A, Brooks A, Lightell Jr D, Woods T . Carotid Plaque Rupture Is Accompanied by an Increase in the Ratio of Serum circR-284 to miR-221 Levels. Circ Cardiovasc Genet. 2017; 10(4). PMC: 5555615. DOI: 10.1161/CIRCGENETICS.117.001720. View

14.

Kalsotra A, Xiao X, Ward A, Castle J, Johnson J, Burge C . A postnatal switch of CELF and MBNL proteins reprograms alternative splicing in the developing heart. Proc Natl Acad Sci U S A. 2008; 105(51):20333-8. PMC: 2629332. DOI: 10.1073/pnas.0809045105. View

15.

Koh W, Pan W, Gawad C, Fan H, Kerchner G, Wyss-Coray T . Noninvasive in vivo monitoring of tissue-specific global gene expression in humans. Proc Natl Acad Sci U S A. 2014; 111(20):7361-6. PMC: 4034220. DOI: 10.1073/pnas.1405528111. View

16.

Byron S, Van Keuren-Jensen K, Engelthaler D, Carpten J, Craig D . Translating RNA sequencing into clinical diagnostics: opportunities and challenges. Nat Rev Genet. 2016; 17(5):257-71. PMC: 7097555. DOI: 10.1038/nrg.2016.10. View

17.

Weiser-Evans M . Smooth Muscle Differentiation Control Comes Full Circle: The Circular Noncoding RNA, circActa2, Functions as a miRNA Sponge to Fine-Tune α-SMA Expression. Circ Res. 2017; 121(6):591-593. PMC: 5679083. DOI: 10.1161/CIRCRESAHA.117.311722. View

18.

Li P, Chen S, Chen H, Mo X, Li T, Shao Y . Using circular RNA as a novel type of biomarker in the screening of gastric cancer. Clin Chim Acta. 2015; 444:132-6. DOI: 10.1016/j.cca.2015.02.018. View

19.

Wu A, Christenson R . Analytical and assay issues for use of cardiac troponin testing for risk stratification in primary care. Clin Biochem. 2013; 46(12):969-978. DOI: 10.1016/j.clinbiochem.2013.04.013. View

20.

Viereck J, Thum T . Circulating Noncoding RNAs as Biomarkers of Cardiovascular Disease and Injury. Circ Res. 2017; 120(2):381-399. DOI: 10.1161/CIRCRESAHA.116.308434. View