Functional analysis of the miR-145/Fascin1 cascade in canine oral squamous cell carcinoma

Oral Dis. 2023 May;29(4):1495-1504. doi: 10.1111/odi.14143. Epub 2022 Feb 13.

Abstract

Objectives: Canine oral squamous cell carcinoma (SCC) often develops in the gingiva and tonsils. The biological behavior of canine oral SCC is similar to that of human head and neck SCC (HNSCC). Inhibiting invasion and metastasis is major importance for the treatment of canine and human HNSCC. In this study, the significance of microRNA (miR)-145 and Fascin1 (FSCN1) in the invasion of canine oral SCC was explored.

Materials and methods: Canine oral SCC tissues and cell lines were used for miR-145 and FSCN1 expression analysis via real-time PCR and immunohistochemistry. Canine oral SCC cell lines were used for in vitro assays.

Results: miR-145 was downregulated while FSCN1 mRNA was upregulated in canine oral SCC. Immunohistochemistry revealed that FSCN1 was upregulated in SCC when compared to normal mucosa. Transfection of canine SCC cells with miR-145 or FSCN1 siRNA suppressed cell growth and attenuated cell migration as well as invasion by inhibiting the epithelial-to-mesenchymal transition. Furthermore, the promoter region of miR-145 was highly methylated in SCC cell lines and tissues.

Conclusion: The expression profile and functions of miR-145 in canine oral SCC are similar to those in human HNSCC. Thus, canine oral SCC may represent a valuable preclinical model for human HNSCC.

Keywords: DNA methylation; MicroRNA-145; canine; fascin1; oral cancer; squamous cell carcinoma.

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell* / pathology
  • Carrier Proteins / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Dogs
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms* / genetics
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Mouth Neoplasms* / genetics
  • Squamous Cell Carcinoma of Head and Neck / genetics

Substances

  • Carrier Proteins
  • FSCN1 protein, human
  • Microfilament Proteins
  • MicroRNAs
  • MIRN145 microRNA, human

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