miR‐141‐3p regulates saturated fatty acid‐induced cardiomyocyte apoptosis through Notch1/PTEN/AKT pathway via targeting PSEN1

Abstract

It has been reported that miR-141-3p levels are markedly upregulated in the cardiomyocytes of obese rats induced by a high-fat diet. However, the role of miR-141-3p in myocardial lipotoxicity remains elusive. In the present study, the role of miR-141-3p in lipotoxic injury of H9c2 cells induced by palmitic acid (PA) and its possible mechanisms were assessed. The results indicated that miR-141-3p was significantly upregulated in PA-induced cardiomyocytes. miR-141-3p inhibitor enhanced the cell viability, reduced the release of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and troponin I (CTN-I), decreased cell apoptosis rate, and repressed the activation of mitochondrial apoptosis pathway in PA-treated H9c2, whereas treatment with miR-141-3p mimics resulted in the opposite effects. Mechanistically, it was further revealed that miR-141-3p could specifically bind to presenilin 1 (PSEN1) 3 0 UTR, and upregulating miR-141-3p levels reduced the expression of PSEN1, thereby inhibiting the activation of the Notch1/PTEN/AKT pathway. Additionally, inhibition of Notch1/AKT signaling pathway by its inhibitor could abrogate the effect of miR-141-3p on mitochondrial-mediated apoptosis induced by PA. In conclusion, the present study demonstrates that miR-141-3p regulates saturated fatty acid-induced cardiomyocyte apoptosis through Notch1/PTEN/AKT pathway via targeting PSEN1, which gains a new insight into the mechanisms of myocardial lipotoxic injury.

Anti-miR-141-3p maintains homeostasis between autophagy and apoptosis by targeting Yy1 in the fetal lumbosacral defecation center of rats

“…miR-141-3p has recently emerged as a key regulator required in the CNS for multiple biological functions, 20 and miR-141-3p serves dual functions in apoptosis and autophagy. 11 , 13 , 15 , 16 However, no previous studies have investigated the effects of miR-141-3p on apoptosis and autophagy in rat fetuses with ARMs. The current findings demonstrate a critical role for miR-141-3p in maintaining homeostasis in the central nervous system of defecation and reveal that miR-141-3p overexpression in ARMs triggered apoptosis and repressed autophagy.…”

“…miR-141-3p upregulation in decidual natural killer cells could be associated with unexplained recurrent spontaneous abortions, 10 and an miR-141-3p inhibitor decreased apoptosis and repressed activation of the mitochondrial apoptosis pathway in palmitic acid-treated H9c2 cells. 11 miR-141-3p overexpression significantly suppressed ectopic endometrial stromal cell proliferation, while promoting apoptosis. 12 Conversely, it is also reported that miR-141-3p inhibition induced apoptosis, suppressed proliferation, and reduced profibrotic markers in hepatic stellate cells by blocking the PTEN-AKT pathway.…”