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  • Title: microRNA-1914, which is regulated by lncRNA DUXAP10, inhibits cell proliferation by targeting the GPR39-mediated PI3K/AKT/mTOR pathway in HCC.
    Author: Sun L, Wang L, Chen T, Yao B, Wang Y, Li Q, Yang W, Liu Z.
    Journal: J Cell Mol Med; 2019 Dec; 23(12):8292-8304. PubMed ID: 31576658.
    Abstract:
    Increasing studies have confirmed that abnormally expressed microRNAs (miRNAs) take part in the carcinogenesis as well as the aggravation of hepatocellular carcinoma (HCC). However, little information is currently available about miR-1914 in HCC. Here, we first confirmed that miR-1914 inhibition in HCC cell lines and tumour specimens correlates with tumour size and histological grade. In a series of functional experiments, miR-1914 inhibited tumour proliferation and colony formation, resulting in cell cycle arrest and increased apoptosis. Moreover, miR-1914 mediated its functional effects by directly targeting GPR39 in HCC cells, leading to PI3K/AKT/mTOR repression. Restoring GPR39 expression incompletely counteracted the physiological roles of miR-1914 in HCC cells. In addition, down-regulation of AKT phosphorylation inhibited the effects of miR-1914 in HCC. Furthermore, the overexpression of lncRNA DUXAP10 negatively correlated with the expression of miR-1914 in HCC; thus, lncRNA DUXAP10 regulated miR-1914 expression and modulated the GPR39/PI3K/AKT-mediated cellular behaviours. In summary, the present study demonstrated for the first time that lncRNA DUXAP10-regulated miR-1914 plays a functional role in inhibiting HCC progression by targeting GPR39-mediated PI3K/AKT/mTOR pathway, and this miRNA represents a novel therapeutic target for patients with HCC.
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