LNCRNA FGD5-AS1 AGGRAVATES MYOCARDIAL ISCHEMIA–REPERFUSION INJURY BY SPONGING MIR-129-5P

Abstract Objectives LncRNA FGD5-AS1 has been found to regulate the pathogenesis of many human diseases. However, the function and regulatory mechanism of lncRNA FGD5-AS1 remains unclear in the pathogenesis of M-I/R injury. This study aims to elucidate the function of lncRNA FGD5-AS1 and the regulatory mechanism of lncRNA FGD5-AS1/miR-129-5p in myocardial ischemia–reperfusion (I/R) injury. Methods To explore the role of lncRNA FGD5-AS1 in myocardial I/R injury, myocardial I/R injury mice model and H/R treated H9c2 cells were established. RT-qPCR and Western blot analysis were used to detect the mRNA and protein expression. Cell viability was detected by MTT assay. Dual luciferase reporter assay was applied to confirm the relationship between lncRNA FGD5-AS1 and miR-129-5p. Results LncRNA FGD5-AS1 was upregulated in myocardial I/R injury mice models and H/R treated H9c2 cells. Functionally, cell proliferation was suppressed in H9c2 cells treated with H/R compared to Normoxia group. Compared with H/R group, knockdown of FGD5-AS1 reduced Bax expression and enhanced Bcl-2 expression. Dual-luciferase reporter assay showed that miR-129-5p mimics reduced the luciferase activity of wt-FGD5-AS1, indicating that miR-129-5p is a direct target of lncRNA FGD5-AS1. Additionally, miR-129-5p alleviated myocardial ischemia/reperfusion injury, while upregulation of lncRNA FGD5-AS1 weakened the protective effect of miR-129-5p on myocardial I/R injury. Conclusion In summary, the upregulation of lncRNA FGD5-AS1 reduced cell proliferation and induced apoptosis in H/R treated cardiomyocytes. More importantly, lncRNA FGD5-AS1 exacerbated myocardial ischemia–reperfusion injury by downregulating miR-129-5p.