LncRNA FGD5-AS1 reduces cardiomyocyte apoptosis and inflammation by modulating Akt and miR-223-3p expression.

OBJECTIVES

Long non-coding RNAs (lncRNAs) are known to be involved in heart development and function. In this study, we aimed to explore the effect of the lncRNA FGD5 antisense RNA 1 (FGD5-AS1) on acute myocardial infarction (AMI) by targeting miR-223-3p.

METHODS

An AMI model was established both in vivo and in vitro. The levels of FGD5-AS1, miR-223-3p and inflammatory factors were detected by real-time quantitative reverse transcription PCR. Cardiomyocyte apoptosis was assessed using TdT-mediated dUTP nick-end labeling assay. The protein levels of cleaved caspase-3, Bcl-2 and Bax were examined using Western blot. Cardiac function was evaluated using hemodynamic analysis and hematoxylin-eosin and Masson's trichrome staining. In addition, an underlying competitive endogenous RNA mechanism was revealed by bioinformatics analysis, dual-luciferase reporter assay and rescue experiments.

RESULTS

We found decreased expression of FGD5-AS1 in AMI. Furthermore, FGD5-AS1 expression significantly decreased the infarct size, improved cardiac performance and attenuated cardiac fibrosis by reducing myocardial apoptosis and inflammation. miR-223-3p was a direct target of FGD5-AS1. Moreover, miRNA-223-3p directly downregulated the expression of phosphorylated Akt in primary neonatal rat cardiomyocytes. Further experiments demonstrated that FGD5-AS1 modulated Akt activity to reduce myocardial injury through miR-223-3p.

CONCLUSION

The FGD5-AS1/miR-223-3p/Akt pathway is involved in AMI, suggesting that FGD5-AS1 may act as a potential biomarker and therapeutic target for AMI.