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MicroRNA-608 acts as a prognostic marker and inhibits the cell proliferation in hepatocellular carcinoma by macrophage migration inhibitory factor

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Tumor Biology

Abstract

Human hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in the world. Research on HCC has recently focused on microRNAs (miRNAs) that play crucial roles in cancer development and progression of HCC. In this study, we aimed to analyze the expression and function of a metastasis-associated microRNA-608 (miR-608) in HCC. Samples of human HCC and matched adjacent normal tissues were surgically removed, and miR-608 expression and the pathological characteristics of HCC were investigated. In this study, we found that miR-608 expression was significantly reduced in HCC and its expression levels were highly associated with tumor size, differentiation, clinical stage, and overall and disease-free survival of HCC. Overexpression of miR-608 in HCC cell lines HepG2 and SK-Hep-1 inhibited cell proliferation by G1 arrest. Macrophage migration inhibitory factor (MIF), a potential target gene of miR-608, was inversely correlated with miR-608 expression in HCC tissues and cell lines. Furthermore, we demonstrated that MIF was directly regulated by miR-608 and the restoration of MIF expression reversed the inhibitory effects of miR-608 on HCC cell proliferation. Taken together, these findings collectively demonstrate that miR-608 exerts its anti-cancer function by directly targeting MIF in HCC, indicating a potential novel prognostic biomarker and therapeutic target for HCC.

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Author notes

    Authors and Affiliations

    1. Department of Pathology, No. 401 Hospital of PLA, 22 Minjiang Road, Qingdao, 266071, China

      Kejia Wang, Li Wei & Wei Zhang

    2. Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai, 200032, China

      Qing Liang

    3. Department of Obstetrics and Gynecology, No. 401 Hospital of PLA, 22 Minjiang Road, Qingdao, 266071, China

      Ping Zhu

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    1. Kejia Wang
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    2. Qing Liang
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    3. Li Wei
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    4. Wei Zhang
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    5. Ping Zhu
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    Correspondence to Wei Zhang or Ping Zhu.

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    All samples were obtained with informed consent, and the study protocol was approved by the Ethics Committee of No. 401 Hospital of PLA.

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    Additional information

    Kejia Wang and Qing Liang contributed equally to this work.

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    Wang, K., Liang, Q., Wei, L. et al. MicroRNA-608 acts as a prognostic marker and inhibits the cell proliferation in hepatocellular carcinoma by macrophage migration inhibitory factor. Tumor Biol. 37, 3823–3830 (2016). https://doi.org/10.1007/s13277-015-4213-5

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    • DOI: https://doi.org/10.1007/s13277-015-4213-5

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