MicroRNA-378 regulates epithelial-mesenchymal transition and metastasis of melanoma by inhibiting FOXN3 expression through the Wnt/β-catenin pathway

MicroRNAs (miRNAs) participate in the development and progression of melanoma. However, while dysregulation of microRNA-378 (miR-378) has been seen in various cancer types, its clinical importance and function in melanoma are poorly elucidated. In this work, miR-378 expression in melanoma and in adjacent non-cancerous tissue was evaluated with a quantitative real-time polymerase chain reaction. A series of assays (wound healing, Transwell, and nude mouse subcutaneous tumor model) were used to investigate the implications of abnormal miR-378 regulation on melanoma cell migration and invasion in vitro, and on tumorigenicity in vivo. Prediction and conformation of the miR-378 target gene was undertaken using bioinformatic analysis and luciferase reporter system. Expression of miR-378 was often increased in melanoma, and shown to potentiate its migration, invasion, and tumorigenicity. miR-378 acted, at least partially, through inhibition of the potential target FOXN3 and via Wnt/beta-catenin pathway activation. The findings indicate that miR-378 triggers melanoma development and progression. This miRNA could be a novel diagnostic and prognostic biological marker and provide utility for targeted treatment of melanoma.