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Article

Inhibition of cell proliferation and metastasis of human hepatocellular carcinoma by miR-137 is regulated by CDC42

  • Authors:
    • Ming Gao
    • Liying Liu
    • Shenglei Li
    • Xudong Zhang
    • Zhiwei Chang
    • Mingzhi Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Oncology, The First People's Hospital of Zhengzhou, Zhengzhou, Henan 450004, P.R. China, Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
  • Pages: 2523-2532
    |
    Published online on: September 9, 2015
       https://doi.org/10.3892/or.2015.4261
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Abstract

In the present study, we evaluated the mechanisms of CDC42 in association with the microRNA-137 (miR-137)-induced inhibition of human hepatocellular carcinoma (HCC). The gene expression levels of miR-137 were evaluated in HCC cell lines. Direct association of miR-137 with its downstream target, cell division control protein 42 (CDC42), was evaluated by dual-luciferase assay, western blot analysis and correlation analysis using clinical tumor samples. In the HCC HuH7 and MHCC97L cell lines, miR-137 was upregulated to inhibit cell proliferation and metastasis in vitro and tumor growth in vivo. CDC42 was overexpressed in the HuH7 and MHCC97L cells to evaluate its effect on the miR-137-mediated antitumor effects. Furthermore, possible crosstalk between CDC42 and another miR-137 target gene, AKT2, was evaluated by co-overexpressing CDC42 and AKT2 in the HuH7 and MHCC97L cells and examining their effects on miR-137-mediated HCC regulation. miR-137 was confirmed to be downregulated in the HCC cell lines. Dual‑luciferase assay showed that CDC42 was directly targeted by miR-137, and western blotting showed that CDC42 was downregulated by miR-137 upregulation in the HuH7 and MHCC97L cells. In human tumors, the expression levels of CDC42 and miR-137 were inversely correlated. The inhibitory effects of miR-137 on HCC proliferation, metastasis and in vivo tumor growth were all ameliorated by CDC42 overexpression. Furthermore, co-overexpression of AKT2 in addition to CDC42 additively reduced the inhibition of miR-137 on HCC proliferation and metastasis, suggesting two independent pathways of CDC42 and AKT2 in miR-137-mediated HCC regulation. Our study demonstrated that CDC42 independently regulated the antitumor effects of miR-137 in human HCC.
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Copy and paste a formatted citation
Spandidos Publications style
Gao M, Liu L, Li S, Zhang X, Chang Z and Zhang M: Inhibition of cell proliferation and metastasis of human hepatocellular carcinoma by miR-137 is regulated by CDC42. Oncol Rep 34: 2523-2532, 2015.
APA
Gao, M., Liu, L., Li, S., Zhang, X., Chang, Z., & Zhang, M. (2015). Inhibition of cell proliferation and metastasis of human hepatocellular carcinoma by miR-137 is regulated by CDC42. Oncology Reports, 34, 2523-2532. https://doi.org/10.3892/or.2015.4261
MLA
Gao, M., Liu, L., Li, S., Zhang, X., Chang, Z., Zhang, M."Inhibition of cell proliferation and metastasis of human hepatocellular carcinoma by miR-137 is regulated by CDC42". Oncology Reports 34.5 (2015): 2523-2532.
Chicago
Gao, M., Liu, L., Li, S., Zhang, X., Chang, Z., Zhang, M."Inhibition of cell proliferation and metastasis of human hepatocellular carcinoma by miR-137 is regulated by CDC42". Oncology Reports 34, no. 5 (2015): 2523-2532. https://doi.org/10.3892/or.2015.4261
Copy and paste a formatted citation
x
Spandidos Publications style
Gao M, Liu L, Li S, Zhang X, Chang Z and Zhang M: Inhibition of cell proliferation and metastasis of human hepatocellular carcinoma by miR-137 is regulated by CDC42. Oncol Rep 34: 2523-2532, 2015.
APA
Gao, M., Liu, L., Li, S., Zhang, X., Chang, Z., & Zhang, M. (2015). Inhibition of cell proliferation and metastasis of human hepatocellular carcinoma by miR-137 is regulated by CDC42. Oncology Reports, 34, 2523-2532. https://doi.org/10.3892/or.2015.4261
MLA
Gao, M., Liu, L., Li, S., Zhang, X., Chang, Z., Zhang, M."Inhibition of cell proliferation and metastasis of human hepatocellular carcinoma by miR-137 is regulated by CDC42". Oncology Reports 34.5 (2015): 2523-2532.
Chicago
Gao, M., Liu, L., Li, S., Zhang, X., Chang, Z., Zhang, M."Inhibition of cell proliferation and metastasis of human hepatocellular carcinoma by miR-137 is regulated by CDC42". Oncology Reports 34, no. 5 (2015): 2523-2532. https://doi.org/10.3892/or.2015.4261
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