Open Access

Integrated analysis of gene expression and DNA methylation changes induced by hepatocyte growth factor in human hepatocytes

  • Authors:
    • Cheng‑Rong Xie
    • Hongguang Sun
    • Fu‑Qiang Wang
    • Zhao Li
    • Yi‑Rui Yin
    • Qin‑Liang Fang
    • Yu Sun
    • Wen‑Xiu Zhao
    • Sheng Zhang
    • Wen‑Xing Zhao
    • Xiao‑Min Wang
    • Zhen‑Yu Yin
  • View Affiliations

  • Published online on: June 22, 2015     https://doi.org/10.3892/mmr.2015.3974
  • Pages: 4250-4258
  • Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Hepatocellular carcinoma (HCC) is the one of most common malignant tumors. The tumor microenvironment has a role in not only supporting growth and survival of tumor cells, but also triggering tumor recurrence and metastasis. Hepatocyte growth factor (HGF), one of the important growth factors in the tumor microenvironment, has an important role in angiogenesis, tumorigenesis and regeneration. However, the exact mechanism by which HGF regulates HCC initiation and development via epigenetic reprogramming has remained elusive. The present study focused on the epigenetic modification and target tumor-suppressive genes of HGF treatment in HCC. Expression profiling and DNA methylation array were performed to investigate the function of HGF and examine global genomic DNA methylation changes, respectively. Integrated analysis of gene expression and DNA methylation revealed potential tumor suppressor genes (TSGs) in HCC. The present study showed the multiple functions of HGF in tumorous and non‑tumorous pathways and global genomic DNA methylation changes. HGF treatment upregulated the expression of DNA methyltransferase 1 (DNMT1). Overexpression of DNMT1 in HCC patients correlated with the malignant potential and poor prognosis of HCC. Furthermore, integration analysis of gene expression and DNA methylation changes revealed novel potential tumor suppressor genes TSGs including MYOCD, PANX2 and LHX9. The present study has provided mechanistic insight into epigenetic repression of TSGs through HGF‑induced DNA hypermethylation.
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September-2015
Volume 12 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Xie CR, Sun H, Wang FQ, Li Z, Yin YR, Fang QL, Sun Y, Zhao WX, Zhang S, Zhao WX, Zhao WX, et al: Integrated analysis of gene expression and DNA methylation changes induced by hepatocyte growth factor in human hepatocytes. Mol Med Rep 12: 4250-4258, 2015.
APA
Xie, C., Sun, H., Wang, F., Li, Z., Yin, Y., Fang, Q. ... Yin, Z. (2015). Integrated analysis of gene expression and DNA methylation changes induced by hepatocyte growth factor in human hepatocytes. Molecular Medicine Reports, 12, 4250-4258. https://doi.org/10.3892/mmr.2015.3974
MLA
Xie, C., Sun, H., Wang, F., Li, Z., Yin, Y., Fang, Q., Sun, Y., Zhao, W., Zhang, S., Zhao, W., Wang, X., Yin, Z."Integrated analysis of gene expression and DNA methylation changes induced by hepatocyte growth factor in human hepatocytes". Molecular Medicine Reports 12.3 (2015): 4250-4258.
Chicago
Xie, C., Sun, H., Wang, F., Li, Z., Yin, Y., Fang, Q., Sun, Y., Zhao, W., Zhang, S., Zhao, W., Wang, X., Yin, Z."Integrated analysis of gene expression and DNA methylation changes induced by hepatocyte growth factor in human hepatocytes". Molecular Medicine Reports 12, no. 3 (2015): 4250-4258. https://doi.org/10.3892/mmr.2015.3974