A novel circPIK3C2A/miR-31-5p/TFRC axis drives ferroptosis and accelerates myocardial injury

Abstract

Iron overload is common in cardiovascular disease, it is also the factor that drives ferroptosis. Noncoding RNAs play an important role in heart disease; however, their regulatory role in iron overload-mediated ferroptosis remains much unknown. In our study, the iron overload model in mice was constructed through a high-iron diet, and ammonium iron citrate treatment was used to mimic iron overload in vitro. We found iron overload induced ferroptosis in cardiomyocytes, which was dependent on the high expression of transferrin receptor (TFRC). MiR-31-5p was downregulated during iron overload; it inhibited cardiomyocyte ferroptosis by targeting TFRC. CircPIK3C2A, a highly expressed circRNA in the heart, was upregulated when iron was overloaded. CircPIK3C2A enhanced the expression of TFRC by sponging miR-31-5p and promoted ferroptosis during iron overload. Our results reveal a novel mechanistic insight into noncoding RNA-based ferroptosis and identify the circPIK3C2A/miR-31-5p/TFRC axis as a promising therapeutic target for myocardial damage.

Keywords

circPIK3C2A / ferroptosis / Iron overload / miR-31-5p / TFRC

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