Underexpressed microRNA-199b-5p targets Hypoxia-Inducible Factor-1α in hepatocellular carcinoma and predicts prognosis of hepatocellular carcinoma patients

Authors

  • Chuanxi Wang,

    1. Department of Oncology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province, China
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  • Bao Song,

    1. Shandong Tumor Hospital and Institute, Jinan, Shandong Province, China
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  • Wei Song,

    1. Department of Oncology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province, China
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  • Jie Liu,

    1. Shandong Tumor Hospital and Institute, Jinan, Shandong Province, China
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  • Aimin Sun,

    1. Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
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  • Dehua Wu,

    1. Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
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  • Huiming Yu,

    1. Department of Oncology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province, China
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  • Jianping Lian,

    1. Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
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  • Longhua Chen,

    Corresponding author
    1. Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
      Dr Longhua Chen, Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China. Email: flchenlh@gmail.com; or Dr Junqing Han, Department of Oncology, Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province, China. Email: hanjunqing1960@126.com
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  • Junqing Han

    1. Department of Oncology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province, China
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  • Conflict of interest: There is no conflict of interest.

  • The first two authors contributed equally to this study.

Dr Longhua Chen, Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China. Email: flchenlh@gmail.com; or Dr Junqing Han, Department of Oncology, Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province, China. Email: hanjunqing1960@126.com

Abstract

Background and Aim:  MicroRNAs are short noncoding RNA molecules that are responsible for the posttranscriptional regulation of target genes. The aim of this study was to determine whether microRNA-199b-5p (miR-199b) plays a role in the progression and prognosis of hepatocellular carcinoma (HCC), and to elucidate whether hypoxia-inducible factor-1α (Hif1α) is regulated by miR-199b.

Methods:  In this study, 35 matched HCCs and cirrhosis tissues were assayed for miR-199b and Hif1α expression. To evaluate the role of miR-199b, we assessed cell proliferation rate and clonogenic survival of miR-199b- or negative control-transfected cells by MTT and clone formation assay, respectively. In addition, the regulation of Hif1α by miR-199b was evaluated by Western blotting and luciferase assay. MiR-199b was downregulated in 77% of HCCs, whereas Hif1α protein was upregulated in 69% of cases. A significant inverse correlation between miR-199b and Hif1α was observed in HCCs.

Results:  Patients with lower levels of miR-199b expression had poorer overall survival and progression-free survival rates, whereas patients with higher levels of miR-199b expression had better survival. Moreover, miR-199b could restrain cell growth and obviously enhance the radiosensitizing effect of HepG2 cells. MiR-199b and pGL3-Hif1α vector-transfected cells showed suppressed Hif1α protein expression and significant reduced luciferase activity.

Conclusions:  Underexpressed miR-199b, which may be via the upregulation of Hif1α in HCCs, is inversely correlated with survival and directly correlated with the malignant status of HCC patients.

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