LncRNA-AK138945 Regulates Myocardial Ischemia-Reperfusion Injury Via the miR-1-GRP94 Signaling Pathway

Abstract Myocardial ischemia-reperfusion injury (MIRI) is one of the main causes of high mortality of cardiovascular diseases (CVD). Long non-coding RNAs (lncRNAs), as a new type of gene expression regulators, play a key role in multiple processes of CVD. In this study, myocardial apoptosis was found to be increased in both MIRI heart and hydrogen peroxide (H2O2) treated myocardial cells. Meanwhile, the level of lncRNA-AK138945 was reduced. At the molecular level, knockdown of lncRNA-AK138945 increased the expression of pro-apoptosis proteins and decreased the expression of anti-apoptosis protein. Mechanically, miR-1a-3p was verified as the target of lncRNA-AK138945, which has been previously confirmed as a target regulator of endoplasmic reticulum stress-related protein GRP94. In addition, knockdown of lncRNA-AK138945 markedly inhibited the expression of GRP94, which further aggravated the apoptosis of cardiomyocytes. Notably, FOXO3 was identified as a transcriptional regulator of lncRNA-AK138945, and overexpression of FOXO3 could promote the expression of lncRNA-AK138945. In conclusion, lncRNA-AK138945 participated in the regulation of MIRI via the miR-1-GRP94 signaling pathway.