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Article

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 / Copyright

    Affiliations: Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China, Department of Gastroenterology, Guangzhou Red Cross Hospital, Ji'nan University, Guangzhou, Guangdong 510180, P.R. China
  • Pages: 494-502
    |
    Published online on: May 18, 2016
       https://doi.org/10.3892/or.2016.4818
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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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Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
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