GATA1 activated lncRNA (Galont) promotes anoxia/reoxygenation-induced autophagy and cell death in cardiomyocytes by sponging miR-338.

The hypernomic autophagy is associated with various cardiovascular diseases. Long noncoding RNAs (lncRNAs) are emerging as important regulators in gene expression, which have been involved in multiple physiological and pathological processes. However, the function of lncRNAs and how they functioned in the autophagy in cardiomyocytes were rarely reported. In this study, we report that a lncRNA, named GATA1 activated lncRNA (Galont), can directly interact with miR-338 and promote ATG5-mediated autophagic cell death in murine cardiomyocytes. First, we found that Galont was upregulated by anoxia/reoxygenation (A/R) stimulus, and it was able to promote autophagy and cell death in cardiomyocytes exposure to A/R. Then, miR-338 was identified as a novel suppressor in autophagy and autophagic cell death. Our results from bioinformatic analysis and luciferase reporter gene assay indicated that ATG5 is a target gene of miR-338. Furthermore, RNA pull-down assays demonstrated that Galont directly interacted with miR-338, and thus promoted ATG5 expression and autophagic cell death. Our findings reveal a novel regulatory circuit in the autophagy in cardiomyocytes, which consists of Galont, miR-338 and ATG5.