Mir-215-5p induces autophagy by targeting PI3K and activating ROS-mediated MAPK pathways in cardiomyocytes of chicken.

In this study, we report that miR-215-5p can promote myocardial autophagy by directly binding to the 3'untranslated region (3'UTR) of phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K). Its target gene PI3K was confirmed by dual luciferase reporter assay, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot in cardiomyocytes. Our results showed that overexpression of miR-215-5p could trigger myocardial autophagy through PI3K-threonine-protein kinase (AKT)-target of rapamycin (TOR) pathway. Further studies revealed that autophagic cell death was dependent on the activation of extracellular signal-regulated kinase1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38 kinase (p38) and generation of reactive oxygen species (ROS) in overexpression of miR-215-5p in cardiomyocytes. On the contrary, miR-215-5p inhibitor can enhance cell survival capacity against autophagy by inhibiting ROS-mitogen-activated protein kinase (MAPK) pathways and activating the PI3K/AKT/TOR pathway in cardiomyocytes. Together, our findings support that miR-215-5p may modulate cell survival programs by regulating autophagy, and miR-215-5p acts as an autophagic regulator in the regulatory feedback loop that regulates cardiomyocyte survival by modulating the PI3K/AKT/TOR pathway and ROS-dependent MAPK pathways. PMID: 30684759 [PubMed - as supplied by publisher]
Source: Journal of Inorganic Biochemistry - Category: Biochemistry Authors: Tags: J Inorg Biochem Source Type: research