MiR-19a mediates gluconeogenesis by targeting PTEN in hepatocytes

Dou,Lin; Wang,Shuyue; Huang,Xiuqing; Sun,Xuelin; Zhang,Yang; Shen,Tao; Guo,Jun; Man,Yong; Tang,Weiqing; Li,Jian

doi:10.3892/mmr.2017.8312

MiR-19a mediates gluconeogenesis by targeting PTEN in hepatocytes

Authors:
- Lin Dou
- Shuyue Wang
- Xiuqing Huang
- Xuelin Sun
- Yang Zhang
- Tao Shen
- Jun Guo
- Yong Man
- Weiqing Tang
- Jian Li
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Affiliations: The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, P.R. China
Published online on: December 19, 2017 https://doi.org/10.3892/mmr.2017.8312
Pages: 3967-3971

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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.

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