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  • Title: MicroRNA-452 promotes stem-like cells of hepatocellular carcinoma by inhibiting Sox7 involving Wnt/β-catenin signaling pathway.
    Author: Zheng Z, Liu J, Yang Z, Wu L, Xie H, Jiang C, Lin B, Chen T, Xing C, Liu Z, Song P, Yin S, Zheng S, Zhou L.
    Journal: Oncotarget; 2016 May 10; 7(19):28000-12. PubMed ID: 27058905.
    Abstract:
    The decrease of microRNA-452 (miR-452) in gliomas promoted stem-like features and tumorigenesis. However, the role of miR-452, especially in regulating cancer stem cells (CSCs) in hepatocellular carcinoma (HCC) remains ambiguous. We enriched stem-like HCC cells by serial passages of hepatospheres with chemotherapeutic agents. Stem-like characteristics including the capabilities of chemo-resistance, stemness-related gene expression profiling, self-renewal, tumorigenicity and metastasis formation were detected. MiR-452 was markedly increased in the chemo-resistant hepatospheres and human HCC tissues. and the overexpression of miR-452 in HCC patients predicted poor overall survival. MiR-452 significantly promoted stem-like characteristics in vitro and in vivo. Further, Sox7 was identified as the direct target of miR-452, which could physically bind with β-catenin and TCF4 in the nucleus and then inhibit the activity of Wnt/β-catenin signaling pathway. Finally, the combined chemotherapy of doxorubicin and all-trans retinoic acid (ATRA) showed dramatically efficiency in suppressing HCC metastasis. These data suggested that miR-452 promoted stem-like traits of HCC, which might be a potential therapeutic target for HCC. The combination of doxorubicin and ATRA might be a promising therapy in HCC management.
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