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

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.

Differentially Expressed Genes, miRNAs and Network Models: A Strategy to Shed Light on Molecular Interactions Driving HNSCC Tumorigenesis

“…In addition to confirming miR-615 [ 79 , 80 ] miR-29c [ 80 , 81 ] and miR-101 [ 80 ] as signatures, the profiling of these elements contributes to dissecting the tangle of interactions underlying HNSCC tumorigenesis. In this view, bipartite networks evidence the upregulation of some genes, including MET [ 82 ], FSCN1 [ 83 ], COL1A1 [ 84 ], and SLC16A1 [ 85 ]. Being targets of downregulated miRNAs, these interactions gain a layer of relevance in promoting HNSCC pathogenesis.The same relevance was noticed for VEGFA and VEGFA-VEGFR2 signaling, i.e., the gene and pathway most targeted by miRNAs downregulated in HNSCC.…”

microRNA-203 inhibits migration and invasion of canine tonsillar squamous cell carcinoma cells by targeting SLUG

“…When 90% confluence was achieved, wounds were made using the head of a 200 μL tip. The detailed procedure was described previously ( 12 ).…”

“…However, only a few studies on the association between miRNAs and EMT have been published in veterinary medicine (9)(10)(11). Although EMT-associated miRNAs have not been validated in CoSCC, miR-145 suppresses the migration of CoSCC cells by targeting Fascin 1 (12).…”