Wnt7a predicts poor prognosis, and contributes to growth and metastasis in tongue squamous cell carcinoma

Oncol Rep. 2019 Mar;41(3):1749-1758. doi: 10.3892/or.2019.6974. Epub 2019 Jan 22.

Abstract

Regional and distant metastases are the principal reasons underlying the high mortality rate associated with tongue squamous cell carcinoma (TSCC); however, the precise molecular mechanisms involved in tongue tumorigenesis remain unknown. The present study aimed to determine the expression and mechanism of regulation of Wnt7a in the growth and metastasis of TSCC. Wnt7a mRNA and protein expression levels were examined in TSCC tissues using reverse transcription‑quantitative polymerase chain reaction and immunohistochemical staining. A loss‑of‑function assay was performed in TSCC cell lines using Wnt7a small interfering RNA or short hairpin RNA, after which, cell proliferation, migration and invasion were analyzed using Cell Counting Kit‑8, tumorigenicity and Transwell assays, respectively. Epithelial‑mesenchymal transition (EMT)‑associated proteins were detected by western blotting. The mRNA and protein expression levels of Wnt7a were significantly upregulated in cancer tissues compared with in the adjacent non‑cancerous tissues. Clinical analysis indicated that Wnt7a expression was associated with T classification, lymph node metastasis and pathological differentiation, and high Wnt7a expression predicted a short recurrence‑free survival for patients with TSCC. Silencing Wnt7a expression suppressed cell proliferation, migration and invasion, and reversed the EMT phenotype in TSCC cell lines. The present study revealed that Wnt7a may be upregulated in TSCC, where it may participate in modulating cell proliferation, migration, invasion and the EMT of TSCC. Therefore, Wnt7a should be considered a novel oncogene, and a potential prognostic and therapeutic target for patients with TSCC.

MeSH terms

  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology*
  • Cell Differentiation / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Lymphatic Metastasis / genetics*
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging / methods
  • Prognosis
  • Tongue Neoplasms / genetics*
  • Tongue Neoplasms / pathology*
  • Up-Regulation / genetics
  • Wnt Proteins / genetics*

Substances

  • WNT7A protein, human
  • Wnt Proteins