MiR-19a mediates gluconeogenesis by targeting PTEN in hepatocytes

  • Lin Dou
    The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, P.R. China
  • Shuyue Wang
    The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, P.R. China
  • Xiuqing Huang
    The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, P.R. China
  • Xuelin Sun
    The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, P.R. China
  • Yang Zhang
    The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, P.R. China
  • Tao Shen
    The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, P.R. China
  • Jun Guo
    The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, P.R. China
  • Yong Man
    The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, P.R. China
  • Weiqing Tang
    The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, P.R. China
  • Jian Li
    The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, P.R. China

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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.

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