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

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.