MicroRNA-494-3p protects rat cardiomyocytes against septic shock via PTEN.

The aim of the present study was to investigate the role of microRNA (miR)-494-3p in myocardial injury in patients with septic shock and the underlying mechanism. A total of 22 patients with sepsis and 17 patients with septic shock were included in the present study. In addition, 20 healthy subjects were recruited as the control group. Peripheral blood was collected from all subjects and a rat cardiomyocyte model of myocardial injury was constructed. Reverse transcription-quantitative polymerase chain reaction was used to measure miR-494-3p expression, while cell counting kit-8 assays were performed to assess cell proliferation. Flow cytometry was performed to investigate cell cycle distribution and apoptosis. Lactate dehydrogenase (LDH) assays were performed to measure LDH levels. ELISA was also performed to measure LDH, tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels in cell culture supernatants. Western blotting was employed to detect phosphatase and tensin homolog (PTEN) protein expression and dual luciferase reporter assays were performed to identify the interaction between miR-494-3p and PTEN mRNA. Reduced miR-494-3p expression was correlated with myocardial damage in patients with septic shock. Sera from patients with septic shock downregulated miR-494-3p expression in rat cardiomyocytes. miR-494-3p overexpression inhibited rat cardiomyocyte injury induced by treatment with sera from patients with septic shock. Furthermore, miR-494-3p overexpression reduced the synthesis and release of TNF-α and IL-6 from rat cardiomyocytes. PTEN knockdown alleviated rat cardiomyocyte injury following treatment with serum from patients with septic shock. PTEN was demonstrated to induce the release of TNF-α and IL-6 from rat cardiomyocytes treated with septic shock serum, while miR-494-3p was demonstrated to bind to the 3'-untranslated seed region of PTEN mRNA to regulate its expression. The results of the present study suggest that miR-494-3p is downregulated in the peripheral blood of patients with septic shock and is negatively correlated with myocardial injury. The present study also indicates that miR-494-3p regulates PTEN expression, inhibits sepsis-induced myocardial injury and protects the function of cardiomyocytes. The protective effect and mechanism of action of miR-494-3p indicate that it has potential for use in the clinical diagnosis and therapy of myocardial damage.