Circular RNA-Expression Profiling Reveals a Potential Role of Hsa_circ_0097435 in Heart Failure via Sponging Multiple MicroRNAs

Abstract

Circular RNAs represent a new type of non-coding RNA molecules that influence the occurrence and development of various human diseases by sponging microRNAs, although their roles in heart failure have not been clarified. In this study, peripheral blood samples from 5 patients with heart failure and 4 healthy volunteers were analyzed by next-generation sequencing (NGS) to screen for differentially expressed Circular RNAs. Fifty-six differentially expressed Circular RNAs were identified, of which 29 were up-regulated and 27 were down-regulated. Dysregulated expression of 6 Circular RNAs was verified by quantitative polymerase chain reaction (PCR) analysis, and hsa_circ_0097435 expression was confirmed to be significantly up-regulated in 40 patients with heart failure. Further study with extracted exosomes showed that hsa_circ_0097435 expression was significantly higher in patients with heart failure. In cardiomyocytes, hsa_circ_0097435 was up-regulated after doxorubicin treatment, promoting cardiomyocyte apoptosis. Hsa_circ_0097435 overexpression promoted cardiomyocyte apoptosis, and silencing hsa_circ_0097435 inhibited apoptosis. Moreover, RNA-pulldown experiments and AGO2-immunoprecipitation experiments revealed that hsa_circ_0097435 potentially served a role in heart failure by sponging multiple microRNAs. Collectively, these results suggest that hsa_circ_0097435 can be used as a biological blood marker and revealed a new pathway involved in regulating myocardial cell injury. Our findings may provide a rational basis for developing new treatments for heart failure.

Circulating Circular RNAs: Novel Biomarkers for Heart Failure

“…Exosomes extracted from peripheral blood samples of patients with HF and healthy patients (control group) were analyzed using next-generation sequencing, and the results indicate that the expression of has_circ_0097435 was upregulated in patients with HF. The high expression of hsa_circ_0097435 in exosomes demonstrates that most hsa_circ_0097435 are encapsulated in the exosomes, confirming that hsa_circ_0097435 is a potential biomarker of HF (Han et al, 2020).…”

“…It will also play roles in HF by sponging multiple miRNAs. (Han et al, 2020) CMs, Cardiomyocytes; DCM, Dilated cardiomyopathy; ICM, Ischemic cardiomyopathy; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; HNCM, Non-obstructive hypertrophic cardiomyopathy; HOCM, Obstructive hypertrophic cardiomyopathy; CAD, Coronary artery disease; ↑: increase, ↓: decrease.…”

<p>Profiling and Integrated Analysis of Differentially Expressed Circular RNAs in Plasma Exosomes as Novel Biomarkers for Advanced-Stage Lung Adenocarcinoma</p>

“…17 A significant characteristic of circRNAs is their ability to adsorb miRNAs and block their binding to noncoding regions of mRNAs to subsequently reverse their inhibitory actions on target-gene transcription. 14 Recent studies show that circRNAs are abundant in exosomes, indicating their potential use for diagnosis and monitoring of pathologies such as polycystic ovary syndrome, 18 cardiovascular disease, 19 traumatic brain injury, 20 and cancers. 21 For example, in patients with osimertinibresistant NSCLC, the level of circ_0002130 in serum exosomes is upregulated.…”

“…Recent studies show that circRNAs are abundant in exosomes, indicating their potential use for diagnosis and monitoring of pathologies such as polycystic ovary syndrome, 18 cardiovascular disease, 19 traumatic brain injury, 20 and cancers. 21 For example, in patients with osimertinib-resistant NSCLC, the level of circ_0002130 in serum exosomes is upregulated.…”

Comprehensive Analysis of Differentially Expressed Profiles of circRNAs in Diabetic Cardiomyopathy

“…Hsa_circ_0097435 is overexpressed in heart failure patients and can sponge multiple microRNAs to accelerate the progression of heart failure. To develop a new therapeutic method, hsa_circ_0097435 can be a promising target [11]. Additionally, circRNAs play a role in atherosclerosis, coronary artery disease, myocardial infarction, as well as cardiomyopathy [12].…”