MiR-19a mediates gluconeogenesis by targeting PTEN in hepatocytes

Abstract

As a member of miR-17-92 miRNA clusters, miR-19a has been considered to regulate hepatic glycogenesis by mediating the PI3K/AKT signaling pathway. However, whether miR-19a serves an important role in gluconeogenesis in hepatocytes remains unknown. In the present study, the impact of miR-19a on gluconeogenesis in HEP1-6 cells and its mechanisms of action were investigated. It was observed that overexpression of miR-19a led to decreased glucose production, accompanied by increased activation of the AKT/FOXO1 signaling pathway and downregulated expression of gluconeogenesis-associated genes, including peroxisome proliferator-activated receptor γ coactivator 1α, phosphoenolpyruvate carboxykinase and glucose 6-phosphatase in the HEP1-6 cells transfected with the miR-19a mimic. In contrast, suppression of miR-19a impaired the activation of the AKT/FOXO1 signaling pathway and increased the expression of gluconeogenesis-associated genes, accompanied by an elevated glucose production. Additionally, phosphatase and tensin homolog (PTEN) was identified as a target of miR-19a and participated in the miR-19a-mediated gluconeogenesis in hepatocytes. These findings provide mechanistic insight into the effects of miR-19a on the regulation of the AKT/FOXO1 signaling pathway and the expression of gluconeogenesis-associated genes. MiR-19a may mediate gluconeogenesis in hepatocytes by downregulating PTEN expression.