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Biomed Res Int. 2014;2014:827415. doi: 10.1155/2014/827415. Epub 2014 Feb 27.

Hepatitis B virus X upregulates HuR protein level to stabilize HER2 expression in hepatocellular carcinoma cells.

Author information

  • 1Department of General Surgery, E-Da Hospital/I-Shou University, Kaohsiung 824, Taiwan ; School of Medicine for International Students, I-Shou University, Kaohsiung 824, Taiwan.
  • 2Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan ; Graduate Institute of Cancer Biology, China Medical University, Taichung 404, Taiwan ; The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University, Taichung 404, Taiwan ; Department of Biotechnology, Asia University, Taichung 413, Taiwan.
  • 3Department of Medical Research, E-Da Hospital/I-Shou University, Kaohsiung 824, Taiwan.
  • 4Department of Medicine and Department of Health Examination, E-Da Hospital/I-Shou University, Kaohsiung 824, Taiwan ; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
  • 5Department of Nutrition, I-Shou University, Kaohsiung 824, Taiwan.
  • 6Department of Biological Science & Technology, I-Shou University, No. 8 Yida Road, Kaohsiung 824, Taiwan.
  • 7Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan.
  • 8Graduate Institute of Cancer Biology, China Medical University, Taichung 404, Taiwan ; The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University, Taichung 404, Taiwan.
  • 9Department of Family Medicine, China Medical University Hospital, Taichung 404, Taiwan.
  • 10Department of Medical Research, E-Da Hospital/I-Shou University, Kaohsiung 824, Taiwan ; Department of Biological Science & Technology, I-Shou University, No. 8 Yida Road, Kaohsiung 824, Taiwan.

Abstract

Hepatitis B virus- (HBV-) associated hepatocellular carcinoma (HCC) is the most common type of liver cancer. However, the underlying mechanism of HCC tumorigenesis is very complicated and HBV-encoded X protein (HBx) has been reported to play the most important role in this process. Activation of downstream signal pathways of epidermal growth factor receptor (EGFR) family is known to mediate HBx-dependent HCC tumor progression. Interestingly, HER2 (also known as ErbB2/Neu/EGFR2) is frequently overexpressed in HBx-expressing HCC patients and is associated with their poor prognosis. However, it remains unclear whether and how HBx regulates HER2 expression. In this study, our data showed that HBx expression increased HER2 protein level via enhancing its mRNA stability. The induction of RNA-binding protein HuR expression by HBx mediated the HER2 mRNA stabilization. Finally, the upregulated HER2 expression promoted the migration ability of HBx-expressing HCC cells. These findings deciphered the molecular mechanism of HBx-mediated HER2 upregulation in HBV-associated HCC.

PMID:
24719890
[PubMed - indexed for MEDLINE]
PMCID:
PMC3955687
Free PMC Article
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