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

Area of Science:

• Cardiovascular Biology
• Molecular Biology
• Epigenetics

Background:

• Cardiac hypertrophy is a significant risk factor for heart failure.
• Circular RNAs (circRNAs) are emerging as key regulators in cardiovascular diseases.
• The specific role of circRftn1 in cardiac hypertrophy remains largely unexplored.

Purpose of the Study:

• To investigate the role of circRftn1 in cardiac hypertrophy.
• To elucidate the underlying molecular mechanism involving the microRNA-1192-tripartite motif 25 and 41 (miR1192-TRIM25/TRIM41) axis.
• To explore the involvement of the NF-κB signaling pathway.

Main Methods:

• Establishment of mouse models for cardiac hypertrophy (abdominal aortic coarctation) and in vitro cell models (neonatal mouse ventricular cardiomyocytes with angiotensin II).
• Next-generation sequencing for differential circRNA expression analysis.
• Bioinformatic prediction of miRNA and mRNA targets.
• Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting for molecular expression analysis.
• Small interfering RNA (siRNA) and miRNA mimic transfections.
• Dual-luciferase reporter assays to validate interactions.

Main Results:

• circRftn1 expression was significantly upregulated in cardiac hypertrophy models (in vivo and in vitro).
• miR-1192 expression was decreased, while its target mRNAs TRIM25 and TRIM41 were upregulated.
• Knockdown of circRftn1 reversed cardiac hypertrophy, decreased TRIM25/TRIM41, and increased miR-1192.
• Dual-luciferase assays confirmed circRftn1 acts as a sponge for miR-1192.
• NF-κB p65 subunit expression paralleled circRftn1 levels, suggesting pathway involvement.

Conclusions:

• circRftn1 promotes cardiac hypertrophy by sponging miR-1192, leading to increased TRIM25/TRIM41 expression.
• The NF-κB signaling pathway is implicated in circRftn1-mediated cardiac hypertrophy.
• circRftn1 represents a potential therapeutic target for cardiac hypertrophy through modulation of the miR-1192-TRIM25/TRIM41 axis.