Open Access

Downregulation of thrombospondin-1 by DNA hypermethylation is associated with tumor progression in laryngeal squamous cell carcinoma

  • Authors:
    • Chuang Huang
    • Xiaohong Zhou
    • Zhenhua Li
    • Hong Liu
    • Yun He
    • Guo Ye
    • Kun Huang
  • View Affiliations

  • Published online on: August 1, 2016     https://doi.org/10.3892/mmr.2016.5580
  • Pages: 2489-2496
  • Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Thrombospondin‑1 (THBS‑1) has been demonstrated to have a complicated role in human cancer and to exert stimulatory and inhibitory effects in different types of tumors. DNA methylation, as the most frequent mechanism for gene silencing, has been widely investigated in regards to the development of tumors. However, the expression levels and methylation status of THBS‑1, and their roles in laryngeal squamous cell carcinoma (LSCC) remain to be elucidated. The present study detected downregulated THBS‑1 mRNA and protein expression levels in LSCC by using reverse transcription-quantitative polymerase chain reaction (PCR) and western blotting, while decreased expression levels of THBS‑1 mRNA and protein were significantly associated with lymph node metastasis and tumor‑node‑metastasis (TNM) stage. Furthermore, aberrant methylation of THBS‑1 was frequently observed in LSCC by methylation‑specific PCR, particularly in tumor tissues from lymph node metastasis or samples from cancer with advanced TNM stage. Furthermore, the current study demonstrated that downregulated expression of THBS‑1 in LSCC was consistent with aberrant methylation of this gene. Treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxy-cytidine in Hep‑2 cells induced demethylation of THBS-1, enhanced THBS‑1 expression, and inhibited the proliferative and invasive ability of Hep‑2 cells. Collectively, the results of the present study suggest that THBS‑1 may exert an inhibitory effect in the development of LSCC. Aberrant methylation was an important reason for the downregulation of THBS‑1 and was involved in the invasion and metastasis of LSCC. Demethylating agents may be effective candidates for the treatment of LSCC.
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September-2016
Volume 14 Issue 3

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

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Spandidos Publications style
Huang C, Zhou X, Li Z, Liu H, He Y, Ye G and Huang K: Downregulation of thrombospondin-1 by DNA hypermethylation is associated with tumor progression in laryngeal squamous cell carcinoma. Mol Med Rep 14: 2489-2496, 2016
APA
Huang, C., Zhou, X., Li, Z., Liu, H., He, Y., Ye, G., & Huang, K. (2016). Downregulation of thrombospondin-1 by DNA hypermethylation is associated with tumor progression in laryngeal squamous cell carcinoma. Molecular Medicine Reports, 14, 2489-2496. https://doi.org/10.3892/mmr.2016.5580
MLA
Huang, C., Zhou, X., Li, Z., Liu, H., He, Y., Ye, G., Huang, K."Downregulation of thrombospondin-1 by DNA hypermethylation is associated with tumor progression in laryngeal squamous cell carcinoma". Molecular Medicine Reports 14.3 (2016): 2489-2496.
Chicago
Huang, C., Zhou, X., Li, Z., Liu, H., He, Y., Ye, G., Huang, K."Downregulation of thrombospondin-1 by DNA hypermethylation is associated with tumor progression in laryngeal squamous cell carcinoma". Molecular Medicine Reports 14, no. 3 (2016): 2489-2496. https://doi.org/10.3892/mmr.2016.5580