Tumor Biology

, Volume 36, Issue 12, pp 9885–9893 | Cite as

Pokemon and MEF2D co-operationally promote invasion of hepatocellular carcinoma

  • Xin Hong
  • Xing-Yu Hong
  • Tao Li
  • Cheng-Yan He
Research Article


Hepatocellular carcinoma (HCC) is one of the most deadly human malignancy, and frequent invasion and metastasis is closely associated with its poor prognosis. However, the molecular mechanism underlying HCC invasion is still not completely elucidated. Pokemon is a well-established oncogene for HCC growth, but its contribution to HCC invasion has not been studied yet. In this paper, Pokemon was found to be overexpressed in MHCC-97H HCC cell line, which possesses higher invasiveness. Downregulation of Pokemon abolished the invasion of MHCC-97H HCC cell lines. Pokemon overexpression was able to enhance the invasion of MHCC-97L cells with lower invasiveness. MEF2D, an oncogene promoting the invasion of HCC cells, was further detected to be upregulated and downregulated when Pokemon was overexpressed and silenced, respectively. Online database analysis indicated that one Pokemon recognition site was located within the promoter of MEF2D. Chromatin co-precipitation, luciferase, and qPCR assays all proved that Pokemon can promote the expression of MEF2D in HCC cells. Restoration of MEF2D expression can prevent the impaired invasion of HCC cells with Pokemon silencing, while suppression of MEF2D abolished the effect of Pokemon overexpression on HCC invasion. More interestingly, MEF2D was also found to increase the transcription of Pokemon by binding myocyte enhancer factor 2 (MEF2) sites within its promoter region, implying an auto-regulatory circuit consisting of these two oncogenes that can promote HCC invasion. Our findings can contribute to the understanding of molecular mechanism underlying HCC invasion, and provided evidence that targeting this molecular loop may be a promising strategy for anti-invasion therapy.


Hepatocellular carcinoma Pokemon MEF2D Invasion 


  1. 1.
    Zhao X, Ning Q, Sun X, Tian D. Pokemon reduces Bcl-2 expression through NF-kappa Bp65: a possible mechanism of hepatocellular carcinoma. Asian Pac J Tro Med. 2011;4(6):492–7.CrossRefGoogle Scholar
  2. 2.
    Lin CC, Zhou JP, Liu YP, Liu JJ, Yang XN, Jazag A, et al. The silencing of Pokemon attenuates the proliferation of hepatocellular carcinoma cells in vitro and in vivo by inhibiting the PI3K/Akt pathway. PLoS One. 2012;7(12), e51916.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Zhu X, Dai Y, Chen Z, Xie J, Zeng W, Lin Y. Knockdown of Pokemon protein expression inhibits hepatocellular carcinoma cell proliferation by suppression of AKT activity. Oncol Res. 2013;20(8):377–81.CrossRefPubMedGoogle Scholar
  4. 4.
    Liu K, Liu F, Zhang N, Liu S, Jiang Y. Pokemon silencing leads to Bim-mediated anoikis of human hepatoma cell QGY7703. Int J Mol Sci. 2012;13(5):5818–31.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Zhang YQ, Xiao CX, Lin BY, Shi Y, Liu YP, Liu JJ, et al. Silencing of Pokemon enhances caspase-dependent apoptosis via fas- and mitochondria-mediated pathways in hepatocellular carcinoma cells. PLoS One. 2013;8(7), e68981.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Jin XL, Sun QS, Liu F, Yang HW, Liu M, Liu HX, et al. MicroRNA 21-mediated suppression of Sprouty1 by Pokemon affects liver cancer cell growth and proliferation. J Cell Biochem. 2013;114(7):1625–33.CrossRefPubMedGoogle Scholar
  7. 7.
    Ding Y, Wang W, Feng M, Wang Y, Zhou J, Ding X, et al. A biomimetic nanovector-mediated targeted cholesterol-conjugated siRNA delivery for tumor gene therapy. Biomaterials. 2012;33(34):8893–905.CrossRefPubMedGoogle Scholar
  8. 8.
    Tian J, Tang ZY, Ye SL, Liu YK, Lin ZY, Chen J, et al. New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis. Br J Cancer. 1999;81(5):814–21.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Yu W, Huang C, Wang Q, Huang T, Ding Y, Ma C, et al. MEF2 transcription factors promotes EMT and invasiveness of hepatocellular carcinoma through TGF-beta1 autoregulation circuitry. Tumour Biol J Int Soc Oncodevelopmental Biol Med. 2014;35(11):10943–51.CrossRefGoogle Scholar
  10. 10.
    Ma L, Liu J, Liu L, Duan G, Wang Q, Xu Y, et al. Overexpression of the transcription factor MEF2D in hepatocellular carcinoma sustains malignant character by suppressing G2-M transition genes. Cancer Res. 2014;74(5):1452–62.CrossRefPubMedGoogle Scholar
  11. 11.
    Zhang QL, Tian DA, Xu XJ. Depletion of Pokemon gene inhibits hepatocellular carcinoma cell growth through inhibition of H-ras. Onkologie. 2011;34(10):526–31.CrossRefPubMedGoogle Scholar
  12. 12.
    Yan Z, Wang J, Wang C, Jiao Y, Qi W, Che S. miR-96/HBP1/Wnt/beta-catenin regulatory circuitry promotes glioma growth. FEBS Lett. 2014;588(17):3038–46.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Vascular SurgeryChina-Japan Union Hospital of Jilin UniversityChang ChunChina
  2. 2.Department of AnesthesiologyChina-Japan Union Hospital of Jilin UniversityChang ChunChina
  3. 3.Department of Pathology and PathophysiologyChina-Japan Union Hospital of Jilin UniversityChang ChunChina

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