Expression and inhibitory role of TIMP-3 in hepatocellular carcinoma

  • Authors:
    • Bo Shen
    • Yingjie Jiang
    • Yuan-Ran Chen
    • Hui-Cong Zheng
    • Wei Zeng
    • Yu-Yuan Li
    • Aoxian Yin
    • Yuqiang Nie
  • View Affiliations

  • Published online on: May 18, 2016     https://doi.org/10.3892/or.2016.4818
  • Pages: 494-502
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Abstract

As a member of the tissue inhibitor of metallo­proteinases (TIMP) family, it has been reported that TIMP-3 is involved in human cancer development. However, the function of TIMP-3 in hepatocellular carcinoma (HCC) development is unclear. We aimed to determine the biological role of TIMP-3 in HCC by evaluating the effects of its methylation status and expression on HCC cell function. TIMP-3 expression in HCC tissues was visibly analyzed by immunohistochemistry. Methylation of the TIMP-3 promoter was evaluated by methylation-specific PCR. Effects of TIMP-3 on HCC cell growth, apoptosis, migration, and invasion were examined by transfecting the TIMP-3-expressing plasmid, pCMV6. TIMP-3 was expressed in non-tumorous live tissue, but silenced or downregulated in 60% of HCC cases (P<0.05). Reduced protein expression of TIMP-3 was associated with reduced tumor differentiation (P=0.003) and increased metastatic activity (P=0.005) in HCC cell lines. Promoter methylation contributed to the TIMP-3 inactivation. Overexpression of TIMP-3 in HCC cell lines suppressed cell proliferation, induced apoptosis, and inhibited migration and invasion in vitro. TIMP-3 expression is suppressed by promoter methylation in HCC. This inhibitory protein acts as a functional tumor suppressor by inhibiting HCC cell proliferation, invasion, and migration and by inducing apoptosis and cell cycle arrest at the G2/M phase.
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July-2016
Volume 36 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Shen B, Jiang Y, Chen Y, Zheng H, Zeng W, Li Y, Yin A and Nie Y: Expression and inhibitory role of TIMP-3 in hepatocellular carcinoma. Oncol Rep 36: 494-502, 2016
APA
Shen, B., Jiang, Y., Chen, Y., Zheng, H., Zeng, W., Li, Y. ... Nie, Y. (2016). Expression and inhibitory role of TIMP-3 in hepatocellular carcinoma. Oncology Reports, 36, 494-502. https://doi.org/10.3892/or.2016.4818
MLA
Shen, B., Jiang, Y., Chen, Y., Zheng, H., Zeng, W., Li, Y., Yin, A., Nie, Y."Expression and inhibitory role of TIMP-3 in hepatocellular carcinoma". Oncology Reports 36.1 (2016): 494-502.
Chicago
Shen, B., Jiang, Y., Chen, Y., Zheng, H., Zeng, W., Li, Y., Yin, A., Nie, Y."Expression and inhibitory role of TIMP-3 in hepatocellular carcinoma". Oncology Reports 36, no. 1 (2016): 494-502. https://doi.org/10.3892/or.2016.4818