Circular RNA Rftn1 Promotes Cardiac Hypertrophy In Vitro and In Vivo by Sponging miRNA-1192 to Upregulate Tripartite Motif Protein 25 and 41.

To verify the role of circular RNA circRftn1 in cardiac hypertrophy and elucidate its potential mechanism via the microRNA-1192-tripartite motif 25 and 41 (miR1192-TRIM25/TRIM41) axis. A mouse model of cardiac hypertrophy was established via abdominal aortic coarctation surgery. An in vitro cell model was generated using neonatal mouse ventricular cardiomyocytes (NMVCs) co-cultured with angiotensin II. Differentially expressed circular RNAs (circRNAs) were identified using next-generation sequencing, and potential target microRNAs (miRNAs) and downstream messenger RNAs (mRNAs) were predicted using bioinformatic analysis. Reverse transcription quantitative polymerase chain reaction and western blotting were used to evaluate the expression of myocardial-associated molecules at the transcriptional and translational levels, respectively. Expression of regulatory molecules was assessed after transfection with small interfering RNAs (siRNAs) or co-culture with miRNA mimics. Dual-luciferase reporter assays were performed to validate interactions between circRNAs and miRNAs. circRftn1 expression was significantly elevated both in vivo and in vitro. Concurrently, the expression of miR-1192 was decreased, whereas its target mRNAs TRIM25 and TRIM41 were markedly upregulated. Knockdown of circRftn1 via siRNA transfection reversed cardiac hypertrophy and led to opposing expression trends of miR-1192 and TRIM25/TRIM41. Dual-luciferase reporter assays confirmed the sponge-like interaction between circRftn1 and miR-1192. By co-culturing NMVCs with miR-1192 mimics, its targets TRIM25/TRIM41 showed significant decreases. Moreover, NF-κB signalling pathway appeared to be involved, as the expression of the p65 subunit paralleled that of circRftn1. circRftn1 may promote cardiac hypertrophy by modulating the miR-1192-TRIM25/TRIM41 axis and NF-κB p65 pathway potentially serving as a downstream pathway.