Circulating Circular RNAs: Novel Biomarkers for Heart Failure

Sun, Chuan; Ni, Ming-ming; Song, Bo; Cao, Lu

doi:10.3389/fphar.2020.560537

Cited by 17 publications

(22 citation statements)

References 94 publications

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“…RNAs) have been implicated in the etiology of cardiac hypertrophy (22). These ncRNAs include miRNAs ( 23) and long ncRNAs, and the long ncRNA category includes circular (circ)RNAs (15,17). A canonical regulatory pathway has been proposed, where circRNA "sponges" and diminishes the concentration of miRNA, and in turn produces an increase in the mRNA which is a demonstrated target of the miRNA (24).…”

Section: Discussionmentioning

confidence: 99%

“…The pathophysiological role of circRNA in cardiac hypertrophy is currently being recognized and the primary mechanism for the circRNA effects has been proposed to be via the canonical regulatory pathway (15,17,22,25). Numerous instances of miRNA in uenced cardiac hypertrophy have been noted (22), and the identi ed miRNA has led investigators to focus on the protein coding genes (through mRNA levels) which would be the entities mediating the terminal events of the pathologic pathway to cardiac hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to tracing the etiology of hypertrophy to a control element (i.e., circRNA) that would be expected to have pleiotropic effects, we also considered that a circRNA could be monitored as a circulating marker for identifying predisposition, severity, or prognosis of at least one element leading to heart failure. Several miRNAs have already been explored as markers for extent of left ventricular function in subjects who have experienced an acute myocardial infarction (17) and Mir-210-5p may provide diagnostic information for ascertaining the presence of cardiovascular remodeling. The question of whether the novel circRNA identi ed in our studies can also function as a diagnostic marker would require some substantial research being initiated by investigations of whether it can be measured in blood or plasma of rats or humans.…”

Section: Discussionmentioning

confidence: 99%

“…HRCR and circSLC8A1-1 have been found to act as sponges for miR-223-5p and miR-133, respectively, and thus regulate hypertrophy (15). Because of the relative stability of circRNA when released into the circulation, measurement of circRNA in blood has also been proposed for use as a biomarker for diagnosing and measuring the severity of various forms of heart disease in humans, and three circRNAs have been reported as potential biomarkers of hypertrophic cardiomyopathy (17).…”

Section: Introductionmentioning

confidence: 99%

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A Novel circRNA Highlights a Path to Cardiac Hypertrophy in Spontaneously Hypertensive Rats.

Tabakoff¹,

Mahaffey²,

Mahaffey³

et al. 2021

Preprint

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BackgroundCardiac hypertrophy can be considered a maladaptive response which in many cases results in heart failure and sudden death. Genetic predisposition to cardiac hypertrophy is ill-defined, but current research has given credence to a role of non-protein-coding RNAs in the development of cardiac hypertrophy.ResultsWe used microarrays, RNA-Seq and quantitative genetics with the spontaneously hypertensive, SHR (SHR/OlaIpcv) rat strain, the normotensive Brown Norway (BN-Lx/Cub) rat strain, and a recombinant inbred (RI) panel of rats (HXB/BXH) derived from these strains to examine the areas of the genome associated with cardiac hypertrophy. We identified circular (circ) RNAs coded within these areas. Of the 122 differentially expressed circRNAs in left ventricle of SHR and BN-Lx rats, three were transcribed from areas corresponding to the QTLs we identified for cardiac hypertrophy using the HXB/BXH rat panel. We then identified microRNAs which are “sponged” by the circ RNAs and the mRNAs which are destabilized by the microRNAs. 265 miRNAs could be identified as targets for the three circRNAs. We focused on the four miRNAs that were also differentially expressed between SHR and BN-Lx rats. One of the miRNAs (Mir-210-5p) was a target of the differentially expressed circ H2afy and circ H2afy was located within the QTL on Chr 17 (genome wide p-value = 0.011). Mir-210-5p has a binding site on the 3’ UTR of DR6, which is differentially expressed and in turn controls the expression level of NFκB. NFκB is an important component of the oxidative stress response leading to hypertrophy.ConclusionsOur work identified a novel circRNA that may be the mediator of a cascade of events that influence a cardiac hypertrophy phenotype. The circRNA and miRNA which we identified may become useful as markers of the risk for cardiac hypertrophy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A Novel circRNA Highlights a Path to Cardiac Hypertrophy in Spontaneously Hypertensive Rats.

Tabakoff¹,

Mahaffey²,

Mahaffey³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…As stated previously, exosomes have been suggested as novel vehicles for intercellular communication in the cardiovascular system ( 71 ). Non-coding RNAs (ncRNAs) have emerged as important regulators of cardiac functions and diseases ( 110 ). So, the ncRNAs as important cargoes of exosomes, the exosomal ncRNAs (Exo-ncRNAs) should play an important role in the AF pathological process and can be used as diagnostic markers or in the treatment approach ( 111 ).…”

Section: Clinical and Biomedical Values Of Exosome In Afmentioning

confidence: 99%

Exosomes and Exosomal Non-coding RNAs Are Novel Promises for the Mechanism-Based Diagnosis and Treatments of Atrial Fibrillation

Chen

Cheng

et al. 2021

Front. Cardiovasc. Med.

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Atrial fibrillation (AF) is the most common arrhythmia worldwide and has a significant impact on human health and substantial costs. Currently, there is a lack of accurate biomarkers for the diagnosis and prognosis of AF. Moreover, the long-term efficacy of the catheter ablation in the AF is unsatisfactory. Therefore, it is necessary to explore new biomarkers and treatment strategies for the mechanism-based AF. Exosomes are nano-sized biovesicles released by nearly all types of cells. Since the AF would be linked to the changes of the atrial cells and their microenvironment, and the AF would strictly influence the exosomal non-coding RNAs (exo-ncRNAs) expression, which makes them as attractive diagnostic and prognostic biomarkers for the AF. Simultaneously, the exo-ncRNAs have been found to play an important role in the mechanisms of the AF and have potential therapeutic prospects. Although the role of the exo-ncRNAs in the AF is being actively investigated, the evidence is still limited. Furthermore, there is a lack of consensus regarding the most appropriate approach for exosome isolation and characterization. In this article, we reviewed the new methodologies available for exosomes biogenesis, isolation, and characterization, and then discussed the mechanism of the AF and various levels and types of exosomes relevant to the AF, with the special emphasis on the exo-ncRNAs in the diagnosis, prognosis, and treatment of the mechanism-based AF.

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Diagnosis of acute myocardial infarction using a combination of circulating circular RNA cZNF292 and clinical information based on machine learning

Zhou

Boeckel

Yao

et al. 2023

MedComm

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Circulating circular RNAs (circRNAs) are emerging as novel biomarkers for cardiovascular diseases (CVDs). Machine learning can provide optimal predictions on the diagnosis of diseases. Here we performed a proof-of-concept study to determine if combining circRNAs with an artificial intelligence approach works in diagnosing CVD. We used acute myocardial infarction (AMI) as a model setup to prove the claim. We determined the expression level of five hypoxia-induced circRNAs, including cZNF292, cAFF1, cDENND4C, cTHSD1, and cSRSF4, in the whole blood of coronary angiography positive AMI and negative non-AMI patients. Based on feature selection by using lasso with 10-fold cross validation, prediction model by logistic regression, and ROC curve analysis, we found that cZNF292 combined with clinical information (CM), including age, gender, body mass index, heart rate, and diastolic blood pressure, can predict AMI effectively. In a validation cohort, CM + cZNF292 can separate AMI and non-AMI

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Circulating Circular RNAs: Novel Biomarkers for Heart Failure

Cited by 17 publications

References 94 publications

A Novel circRNA Highlights a Path to Cardiac Hypertrophy in Spontaneously Hypertensive Rats.

A Novel circRNA Highlights a Path to Cardiac Hypertrophy in Spontaneously Hypertensive Rats.

Exosomes and Exosomal Non-coding RNAs Are Novel Promises for the Mechanism-Based Diagnosis and Treatments of Atrial Fibrillation

Diagnosis of acute myocardial infarction using a combination of circulating circular RNA cZNF292 and clinical information based on machine learning

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